Coordinated use of respiratory and cardiac therapies for sleep disordered breathing

ABSTRACT

Methods and systems involve coordinating therapies used for treating disordered breathing. Disordered breathing therapies may include cardiac electrical stimulation therapy and external respiratory therapy as well as other therapies for treating disordered breathing in a patient. The therapies delivered to the patient may be coordinated to enhance effectiveness of the therapy, to reduce therapy interactions, to improve patient sleep, or to achieve other therapeutic goals.

RELATED PATENT DOCUMENTS

This application is a continuation of U.S. patent application Ser. No.12/545,670, filed on Aug. 21, 2009, to issue as U.S. Pat. No. 8,104,470,which is a continuation of U.S. patent application Ser. No. 10/930,979,filed on Aug. 31, 2004, now U.S. Pat. No. 7,591,265, which claims thebenefit of Provisional Patent Application Ser. No. 60/504,561, filed onSep. 18, 2003, to which priority is claimed pursuant to 35 U.S.C. §120and 35 U.S.C. §119(e), respectively, and which are hereby incorporatedherein by reference in their entireties.

FIELD OF THE INVENTION

The present invention relates generally to providing therapy for sleepdisordered breathing.

BACKGROUND OF THE INVENTION

The human body functions through a number of interdependentphysiological systems controlled through various mechanical, electrical,and chemical processes. The metabolic state of the body is constantlychanging. For example, as exercise level increases, the body consumesmore oxygen and gives off more carbon dioxide. The cardiac and pulmonarysystems maintain appropriate blood gas levels by making adjustments thatbring more oxygen into the system and dispel more carbon dioxide. Thecardiovascular system transports blood gases to and from the bodytissues. The respiration system, through the breathing mechanism,performs the function of exchanging these gases with the externalenvironment. Together, the cardiac and respiration systems form a largeranatomical and functional unit denoted the cardiopulmonary system.

Various disorders may affect the cardiovascular, respiratory, and otherphysiological systems. For example, heart failure (HF) is a clinicalsyndrome that impacts a number of physiological processes. Heart failureis an abnormality of cardiac function that causes cardiac output to fallbelow a level adequate to meet the metabolic demand of peripheraltissues. Heart failure is usually referred to as congestive heartfailure (CHF) due to the accompanying venous and pulmonary congestion.Congestive heart failure may have a variety of underlying causes,including ischemic heart disease (coronary artery disease), hypertension(high blood pressure), and diabetes, among others.

Disordered breathing is a respiratory system condition that affects asignificant percentage of patients between 30 and 60 years. Disorderedbreathing, including apnea and hypopnea, may be caused, for example, byan obstructed airway, or by derangement of the signals from the braincontrolling respiration. Sleep disordered breathing is associated withexcessive daytime sleepiness, systemic hypertension, increased risk ofstroke, angina and myocardial infarction. Disordered breathing isrelated to congestive heart failure and can be particularly serious forpatients concurrently suffering from cardiovascular deficiencies.

Various types of disordered breathing have been identified, including,apnea (interrupted breathing), hypopnea (shallow breathing), tachypnea(rapid breathing), hyperpnea (heavy breathing), and dyspnea (laboredbreathing). Combinations of the respiratory cycles described above maybe observed, including, for example, periodic breathing andCheyne-Stokes respiration (CSR). Cheyne-Stokes respiration isparticularly prevalent among heart failure patients, and may contributeto the progression of heart failure.

Effective approaches to treating sleep disordered breathing are needed.The present invention fulfills these and other needs, and addressesother deficiencies of prior art implementations and techniques.

SUMMARY OF THE INVENTION

Various embodiments of present invention involve methods and systems forcoordinating sleep disordered breathing therapies. In accordance withone embodiment, a method for treating disordered breathing includescontrolling an patient-external respiratory therapy delivered to apatient and controlling a cardiac therapy delivered to the patient. Thepatient-external respiratory therapy and the cardiac therapy arecoordinated to treat the disordered breathing.

In accordance with another embodiment of the invention, a medical systemincludes a respiratory therapy controller configured to control anexternal respiratory therapy delivered to a patient and a cardiactherapy controller configured to deliver a cardiac therapy to thepatient. The system also includes a processor, coupled to therespiratory therapy controller and the cardiac therapy controller. Theprocessor is configured to coordinate delivery of the externalrespiratory therapy and the cardiac therapy to treat disorderedbreathing.

The above summary of the present invention is not intended to describeeach embodiment or every implementation of the present invention.Advantages and attainments, together with a more complete understandingof the invention, will become apparent and appreciated by referring tothe following detailed description and claims taken in conjunction withthe accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIGS. 1A-B are flowcharts illustrating methods that involve controllingand coordinating cardiac therapy and respiratory therapy in order tocoordinate sleep disordered breathing therapy in accordance withembodiments of the invention;

FIG. 2 is a block diagram of a medical system that may be used toimplement coordinated disordered breathing therapy in accordance withembodiments of the invention;

FIG. 3 illustrates a block diagram of a medical system that may be usedto provide coordinated therapies for controlling sleep disorderedbreathing in accordance with embodiments of the invention;

FIGS. 4A and 4B are partial views of an implantable device that mayinclude circuitry for sensing and monitoring one or more patientconditions used for providing therapy coordination information for sleepdisordered breathing in accordance with embodiments of the invention;

FIG. 5 is a block diagram of a patient-external respiratory therapydevice that may be utilized in a system providing coordinated sleepdisordered breathing therapy in accordance with embodiments of theinvention;

FIG. 6 is a block diagram of an implantable medical device including acardiac therapy pulse generator that may be utilized in a systemdelivering coordinated disordered breathing therapy in accordance withembodiments of the invention;

FIG. 7 is a graph of a respiration signal measured by a transthoracicimpedance sensor that may be utilized for monitoring parameters ofbreathing therapy in accordance with embodiments of the invention;

FIG. 8 is a flowchart illustrating a method of detecting sleep accordingto embodiments of the invention;

FIG. 9 is a flowchart illustrating a sleep detection method based onsignals from an accelerometer and a minute ventilation sensor inaccordance with embodiments of the invention;

FIG. 10A is a graph of an accelerometer signal indicating patientactivity level that may be used for sleep detection in accordance withembodiments of the invention;

FIG. 10B is a graph of a patient's heart rate and sensor indicated ratethat may be used for sleep detection in accordance with an embodiment ofthe invention;

FIG. 11 is a graph of baseline trending for a minute ventilation signalused for sleep detection in accordance with embodiments of theinvention;

FIG. 12 illustrates adjustment of an accelerometer sleep threshold usingan MV signal in accordance with embodiments of the invention

FIG. 13 is a respiration signal graph illustrating respiration intervalsused for disordered breathing detection according to embodiments of theinvention;

FIG. 14 is a graph of a respiration signal illustrating variousintervals that may be used for detection of apnea in accordance withembodiments of the invention;

FIGS. 15A and 15B are respiration graphs illustrating normal respirationand abnormally shallow respiration utilized in detection of disorderedbreathing in accordance with embodiments of the invention;

FIG. 16 is a flowchart illustrating a method of apnea and/or hypopneadetection according to embodiments of the invention;

FIG. 17 is a respiration graph illustrating a breath interval utilizedin connection with disordered breathing detection in accordance withembodiments of the invention;

FIG. 18 is a respiration graph illustrating a hypopnea detectionapproach in accordance with embodiments of the invention;

FIGS. 19 and 20 provide charts illustrating classification of individualdisordered breathing events and series of periodically recurringdisordered breathing events, respectively, in accordance withembodiments of the invention;

FIGS. 21A-E are graphs illustrating respiration patterns that may bedetected as disordered breathing episodes in accordance with embodimentsof the invention;

FIG. 22 is a flowchart of a method for detecting disordered breathing inaccordance with embodiments of the invention; and

FIGS. 23 and 24 are flowcharts illustrating methods of adjustingcoordinated sleep disordered breathing therapy according to embodimentsof the invention.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail below. It is to be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the invention isintended to cover all modifications, equivalents, and alternativesfalling within the scope of the invention as defined by the appendedclaims.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

In the following description of the illustrated embodiments, referencesare made to the accompanying drawings which form a part hereof, and inwhich are shown by way of illustration, various embodiments by which theinvention may be practiced. It is to be understood that otherembodiments may be utilized, and structural and functional changes maybe made without departing from the scope of the present invention.

Sleep disordered breathing may be more effectively monitored and/ortreated using a coordinated approach. Various embodiments of theinvention are implemented using medical systems employing two or morepatient-external and/or patient-internal medical devices. The medicaldevices may communicate or otherwise operate in concert to providecoordinated disordered breathing therapy.

Embodiments of the invention are directed to methods and systemsutilizing a plurality of therapies to treat sleep disordered breathing.The therapies include, at least, an external respiratory therapy andcardiac electrical stimulation therapy. Other therapies may also becooperatively utilized.

Delivery of the plurality of therapies may be coordinated to achievevarious therapeutic goals, e.g., to enhance overall therapy efficacy, toreduce impact to the patient, to avoid therapy interactions, amongothers. According to one example, coordination of therapies may involveshifting the therapy burden from one type of therapy to another type oftherapy in response to events or conditions. In one implementation,shifting the burden from one type of therapy to another type of therapymay involve initiating or increasing a first type of disorderedbreathing therapy and terminating or decreasing a second type ofdisordered breathing therapy. Another example of coordinating therapymay involve using one type of therapy to treat one type of disorderedbreathing, and using another type of therapy to treat another type ofdisordered breathing.

Various types of therapies have been used to treat sleep disorderedbreathing. Positive airway pressure devices, e.g., continuous positiveairway pressure (CPAP) devices are among the most frequently usedmechanical respiration therapy devices employed for treating sleepdisordered breathing. Sleep disordered breathing has also been treatedusing muscle and/or nerve stimulation therapy. For example, a treatmentfor obstructive sleep apnea involves electrical activation of the tonguemuscles. The hypoglossal (HG) nerve innervates the protrusor andretractor tongue muscles. In one approach, an appropriately appliedelectrical stimulation to the hypoglossal nerve, for example, mayprevent backward movement of the tongue, thus preventing the tongue fromobstructing the airway.

Central sleep apnea may also be treated by phrenic nerve pacing, alsoreferred to as diaphragmatic pacing. Phrenic nerve pacing uses anelectrode implanted in the chest to stimulate the phrenic nerve. Thephrenic nerve is generally known as the motor nerve of the diaphragm. Itruns through the thorax, along the heart, and then to the diaphragm.Diaphragmatic pacing involves the use of electronic stimulation of thephrenic nerve to control the patient's diaphragm and induce arespiratory cycle. Pacing the phrenic nerve may be accomplished bysurgically placing a nerve cuff on the phrenic nerve, and thendelivering an electric stimulus. The electric stimulus of the phrenicnerve then causes the diaphragm to induce a respiratory cycle.

Recently, cardiac pacing therapy has been used as a therapy fordisordered breathing. Cardiac pacing therapy may be implemented using animplanted electrical pulse generator coupled to endocardiac leadsinserted into one or more heart chambers. Cardiac pacing for sleepdisordered breathing treatment may include pacing one or more heartchambers, and may involve pacing at a rate above a lower rate limitduring sleep and/or during episodes of disordered breathing, forexample. Other forms of cardiac pacing such as cardiac resynchronizationtherapy, biventricular pacing can be delivered to the patient to treatdisordered breathing.

Another cardiac therapy that can be adapted to mitigate disorderedbreathing involves non-excitatory stimulation therapy. In one example,non-excitatory cardiac stimulation therapy involves electricalstimulation of one or more heart chambers, e.g., the left and/or rightventricles, or other cardiac sites, at an energy level below a capturethreshold. In another example, non-excitatory cardiac stimulationtherapy involves cardiac electrical stimulation delivered to one or moreheart chambers during absolute refractory periods of the cardiac tissue.The non-excitatory stimulation may improve cardiac contractility. Thenon-excitatory cardiac stimulation therapy may be used alone or incombination with cardiac pacing therapy to provide a comprehensivetherapy regimen for patients with CHF and disordered breathing such asCheyne-Stokes respiration.

Cardiac therapy has also been used to mitigate disordered breathingusing methods that involve overdrive cardiac pacing of one or more atriaor one or more ventricles.

Drug therapy may also be used to treat disordered breathing. Drugs maybe delivered to the patient through one or more automaticallycontrollable drug delivery devices, e.g., a drug pump, a controllablenebulizer, or an electrically activated drug patch, for example.

As illustrated in the flowchart of FIG. 1A, embodiments of the inventionare directed to an automated method for controlling disordered breathingtherapy delivered to a patient. The method involves controlling 110delivery of an external respiratory therapy and controlling delivery 120of a cardiac therapy. The external respiratory therapy and the cardiactherapy are coordinated 130 to treat disordered breathing.

In various implementations, one or more conditions affecting the patientand associated with disordered breathing and/or disordered breathingtherapy may be sensed. The sensed conditions may be used, for example,to detect and/or predict disordered breathing episodes, determine aseverity of disordered breathing, detect sleep, assess sleep quality,evaluate an efficacy of the therapy, evaluate an impact of the therapyon the patient, determine therapy interactions, determine patient usageof the therapies, among other factors. Coordination of the therapies maybe performed based on the sensed conditions. The therapies may beadjusted to enhance therapy effectiveness, to reduce an impact of thetherapy, to avoid or reduce therapy interactions, and/or to accomplishother therapeutic goals.

According to embodiments presented herein, a coordinating processor unitis used to generate control signals used for controlling disorderedbreathing therapies delivered to the patient. In one embodiment, thecoordinating unit may transmit control signals directly to an externalrespiratory therapy device and a cardiac therapy device. The controlsignals may be used by the respective therapy devices to automaticallyadjust the therapy delivered to the patient. In another embodiment, boththe coordinating unit and the therapy devices may be communicativelycoupled to a separate medical device, such as a device programmer orpatient management system. The coordinating unit may transmit controlinformation indirectly to the therapy devices through a deviceprogrammer or patient management system.

Advanced patient management (APM) systems involve a system of medicaldevices that are accessible through various communications technologies.Medical information may be transmitted to a remote patient managementserver from the various medical devices. The medical information may beanalyzed and used to diagnose and/or monitor disease progression, todetermine and control delivery of appropriate therapies for the patient,and/or for other medical purposes. Advanced patient managementtechniques, aspects of which may be utilized in systems and methodsproviding coordinated sleep disordered breathing therapy in accordancewith embodiments of the invention, are further described in U.S. Pat.Nos. 6,336,903, 6,312,378, 6,270,457, and 6,398,728 which areincorporated herein by reference.

In one embodiment of the invention, a sensor system may sense one ormore conditions related to disordered breathing. Disordered breathingevents may be detected based on the sensed conditions. Characteristicsof the disordered breathing events such as severity, frequency, and/orduration, may be determined. Determination of the one or morecharacteristics of the sleep disordered breathing events may involvecalculation of one or more indices characterizing the disorderedbreathing events. The indices may include, for example, anapnea/hypopnea index (AHI) and/or a percent time in periodic breathing(% PB), among other indices. The external respiratory therapy and thecardiac therapy maybe coordinated based on the characteristics of thedisordered breathing events.

In accordance with an embodiment of the invention, illustrated in theflowchart of FIG. 1B, coordination of disordered breathing therapies,including an external respiratory therapy and a cardiac electricalstimulation therapy, may be implemented using circuitry disposed withinthe housing of an implantable cardiac rhythm management (CRM) device.The therapies delivered to the patient may be coordinated based on avariety of factors, including therapy effectiveness and/or impact of thetherapy on the patient. In this embodiment, the external respiratorytherapy is delivered by a continuous positive airway pressure (CPAP)device. The cardiac therapy comprises cardiac electrical stimulationtherapy for treating disordered breathing delivered by the CRM device.

One or more sensors may be employed to sense conditions related todisordered breathing and/or disordered breathing therapy, including, forexample, the effectiveness of the breathing therapy and/or the impact ofthe therapy on the patient. The sensors may be coupled to the CPAPdevice, the CRM device, or a first set of sensors may be coupled to theCPAP device and a second set coupled to the CRM device. The coordinatingunit within the CRM device receives the signals from the sensors,determines therapy effectiveness and/or impact, and coordinates therapydelivered by the CPAP and CRM devices.

In one example, a condition modulated by patient respiration may besensed 174 and a respiration waveform signal generated. Circuitrydisposed within the housing of the CRM device may detect 176 disorderedbreathing episodes based on the respiration signal. The coordinationunit may determine therapy effectiveness based on the severity,frequency and/or duration of sleep disordered breathing episodesexperienced by the patient. In one implementation, coordinationcircuitry disposed within the CRM device may calculate 178 anapnea/hypopnea index (AHI) indicative of the frequency of disorderedbreathing episodes. The effectiveness of the sleep disordered breathingtherapy may be determined 180 based on the sleep disordered breathingindex. If the AHI is relatively low, the breathing therapy may bedetermined to be effective. If the AHI is relatively high, then thebreathing therapy may be determined to be ineffective.

A CPAP device typically includes a respiratory mask, e.g., a nasal offacial mask, worn by the patient to facilitate delivery or air or othergas to the patient's airway. The respiratory mask may be inconvenientand/or uncomfortable for the patient to wear and may keep the patientawake. Further, delivery of positive airway pressure may inhibit sleep,or cause the patient to arouse frequently. Information about these sideeffects of the breathing therapy may be helpful in coordinating atherapy regimen for the patient.

Impact of the external breathing therapy and/or cardiac electricalstimulation therapy may be determined based on the patient's sleepquality. Sensors coupled to the coordination processor within the CRMdevice are configured to sense 182 one or more conditions related tosleep. The sleep related conditions are used to detect 184 sleep and/orarousals from sleep. The coordination processor within the CRM devicedetermines 186 the impact of the therapies on the patient by monitoringthe patient's sleep. For example, the coordination processing maymonitor the total time the patient spends sleeping, the number ofarousals experienced by the patient in one night, the number of arousalscorrelated to sleep disordered breathing events, the number of arousalscorrelated to therapy delivery, and/or the depth of the arousals. Invarious implementations the coordination processor may calculate variousindices characterizing sleep and/or one or more composite indices basedon indices related to sleep and indices related to sleep disorderedbreathing. In one example, the monitoring unit calculates the number ofarousals experienced by the patient per hour (A/h).

Therapy coordination may be accomplished 188 based on the therapyeffectiveness and impact information. Control signals may be transmittedfrom the coordinating processor unit to the therapy units of the CRM andCPAP devices. One or both of the therapies delivered by the CRM and CPAPdevices may be adjusted to enhance therapy effectiveness and/or reduceside effects.

In various examples, coordinated disordered breathing therapy mayinvolve adjusting the cardiac electrical stimulation therapy fordisordered breathing, adjusting the neurostimulation therapy fordisordered breathing and/or adjusting the external respiration therapyfor disordered breathing. According to this scenario, a disorderedbreathing therapy coordination processor may distribute the burden ofdisordered breathing therapy between one or more therapy devices.

In one implementation, certain types of therapy may be used forpredetermined periods of time. For example, a predetermined level ofcardiac and/or nerve stimulation therapy may be used prior to thepatient falling asleep. The therapy burden may be shifted to theexternal respiratory therapy device after sleep has been detected. Inone implementation, the therapy burden may be distributed based ondetected arousals. For example, if the delivery of one type of therapycauses the patient to arouse from sleep, the therapy burden may beshifted to other types of therapy to enhance the patient's sleepquality. Alternatively, rather than shifting to other types of therapy,therapy parameters of a particular therapy may be adjusted to providemore restful sleep. For example, an external respiratory therapypressure may be adjusted downward to provide a disordered breathingtherapy that is more comfortable to the patient and allows the patientto sleep better. In one implementation, the respiratory therapy pressuremay be adjusted downward and the pacing rate may be adjusted upward tomaintain effectiveness of the therapy while reducing an impact on thepatient.

In another implementation, the therapy burden may be distributed basedon therapy efficacy. In one scenario, the therapy controller may addtherapies to the overall disordered breathing therapy regimen to improvetherapy efficacy. For example, if the therapy coordination processordetermines that disordered breathing is occurring despite the use of onetype of therapy, additional one or more types of therapy may be added tothe regimen in order to treat disordered breathing.

In one scenario, the disordered breathing therapy burden may bedistributed based on device usage. For example, if the patient does notuse the external respiratory therapy device, then the disorderedbreathing therapy coordination processor may signal a CRM device and/oran external respiratory therapy device to initiate or increase the levelof therapy delivered by the CRM device, the external respiratory therapydevice, and/or other therapy devices.

In one embodiment, the coordination processor may coordinate thedisordered breathing therapy to enhance therapy efficacy while adjustingor avoiding a therapy impact. The coordination processor may acquireinformation related to the sensed conditions and may evaluate therapyefficacy and/or impact on the patient, i.e., side effects of thetherapy, based on the sensed conditions. The coordination processor maymodify the therapy delivered by one or more therapy devices to enhancetherapy efficacy while reducing or avoiding side effects. Thecoordination processor may modify the therapy to reduce interactionsbetween the disordered breathing therapy and other types of therapiesdelivered to the patient, e.g., neurostimulation for anti-hypertensivetherapy and/or cardiac rhythm management. The coordination processor maymodify the therapy to reduce interactions between different types ofdisordered breathing therapies, for example. The therapy controller maymodify a therapy to increase the useable lifetime of an implantabledevice.

FIG. 2 is a block diagram of a medical system 200 that may be used toimplement coordinated disordered breathing therapy in accordance withembodiments of the invention. The medical system 200 may include, forexample, a cardiac therapy device 210, an external respiratory therapydevice 220 and an advanced patient management system 230.

The cardiac therapy device 210 may be a fully or partially implantabledevice including a therapy unit 212 coupled to one or more patientinternal sensors 241, patient-external sensors 242, patient input device243, and/or other information systems 244. The therapy unit 212 usesinputs from the patient internal sensors 241, patient-external sensors242, patient input device 243, and/or other information systems 244 tomonitor one or more patient conditions. In one embodiment, a therapycoordination processor 216 having circuitry disposed within theimplantable housing of the cardiac therapy device 210 uses the sensedconditions to process and coordinate patient information that may beused to adjust the sleep disordered breathing therapy delivered to thepatient by the external respiratory therapy device 220 and the cardiactherapy device 210. In another embodiment, the therapy coordinationprocessor 216 is disposed within a separate device, such as a patientmanagement server 230 of an APM system. In yet another embodiment, thetherapy coordination processor 216 may be disposed within the externalrespiratory therapy device 220.

The external respiratory therapy device 220 may be positioned on thepatient, near the patient, or in any location external to the patient.It is understood that a portion of a patient-external therapy device maybe positioned within an orifice of the body, such as the nasal cavity ormouth, yet can be considered external to the patient (e.g., mouthpieces/appliances, tubes/appliances for nostrils, or temperature sensorspositioned in the ear canal).

The external respiratory therapy device 220 and/or the APM device 230may be coupled to one or more sensors 245, 246 and/or other informationdevices 247, 248. Information from the sensors 245, 246, e.g., flowsensors, pressure sensors, and/or other devices 247, 248 coupled to theexternal respiratory therapy device 220 and/or the APM device 230 may becombined with the information acquired by the cardiac therapy device 210to develop and deliver a coordinated therapy.

In one implementation, the cardiac therapy device 210 is coupled to oneor more patient-internal sensors 241 that are fully or partiallyimplantable within the patient. The cardiac therapy device 210 may alsobe coupled to patient-external sensors 242 positioned on, near, or in aremote location with respect to the patient. The patient-internal 241and patient-external 242 sensors may be used to sense variousparameters, such as physiological or environmental parameters that maybe used to develop coordinated disordered breathing therapies.

In some situations, the patient-internal sensors 241 may be coupled tothe cardiac therapy device 210 through internal leads. In one example,an internal endocardial lead system may be used to couple cardiacelectrodes to a cardiac therapy device 210 such as an implantablepacemaker or other cardiac device.

In some situations, one or more patient-internal sensors 241, patientexternal sensors 242, patient input devices 243, and/or otherinformation systems 244 may be equipped with transceiver circuitry tosupport wireless communications with the cardiac therapy device 210.Similarly, one or more patient-internal sensors 245, patient externalsensors 246, patient input devices 247, and/or other information systems248 may be communicate wirelessly with the external respiratory therapydevice 220.

The cardiac therapy device 210 and/or the external respiratory therapydevice 220 may be coupled to patient-input devices 243, 247. Thepatient-input devices 243, 247 may be used to allow the patient tomanually transfer information to the cardiac therapy device 210 and/orthe external respiratory therapy device 220. The patient input devices243, 247 may be particularly useful for inputting information concerningpatient perceptions, such as how well the patient feels, and informationsuch as patient smoking, drug use, or other activities that are notautomatically sensed or detected by the medical sensors 241, 242, 245,246 or information systems 244, 248.

The cardiac therapy device 210 and/or the external respiratory therapydevice 220 may be connected to one or more information systems 244, 248,for example, a database system or server that acquires and/or storesinformation useful in connection with coordinating therapy functions ofthe cardiac therapy device 210 and the external respiratory therapydevice 220. For example, the cardiac therapy device 210 or the externalrespiratory therapy device 220 may be coupled through a network to aninformation system server that provides information about environmentalconditions affecting the patient, e.g., the pollution index for thepatient's location.

In one embodiment, the cardiac therapy device 210 and the externalrespiratory therapy device 220 may be communicatively coupled through awireless link. For example, the cardiac therapy device 210 and externalrespiratory therapy device 220 may be coupled through a short-rangeradio link, such as Bluetooth or a proprietary wireless link. Thecommunications link may facilitate uni-directional or bi-directionalcommunication between the cardiac therapy device 210 and the externalrespiratory therapy device 220. Data and/or control signals may betransmitted between the cardiac therapy device 210 and externalrespiratory therapy device 220 and can be used to modify disorderedbreathing therapy. For example, sensors of an external respiratorytherapy device 220 may sense a set of patient conditions and therespiratory therapy device 220 may transmit the patient conditions to acoordination processor configured as a component of the cardiac therapydevice 210. Alternatively, sensors of cardiac device 210 may sense a setof patient conditions and the cardiac therapy device 210 may transmitthe patient conditions to a coordination processor configured as acomponent of the respiratory therapy device 220.

In an embodiment of the invention, the cardiac therapy and externalrespiratory therapy devices 210, 220 may be used within the structure ofan advanced patient management (APM) system 230. As previouslydiscussed, advanced patient management systems involve a system ofmedical devices that are accessible through various communicationstechnologies. For example, patient data may be downloaded from one ormore of the medical devices periodically or on command, and stored at apatient information server. The physician and/or the patient maycommunicate with the medical devices and the patient information server,for example, to acquire patient data or to initiate, terminate or modifytherapy.

The APM patient information server 230 may be used to download and storedata collected by the cardiac therapy device 210 and/or the externalrespiratory therapy device 220. In one implementation, the cardiactherapy device 210 and/or the external respiratory therapy device 220may be communicatively coupled to device programmers 260, 270. Theprogrammer 260 may provide indirect communication between the cardiactherapy device 210 and the patient information server 230. Theprogrammer 270 may provide indirect communication between the externalrespiratory therapy device 220 and the patient information server 230.Information received by patient information server 230 can be processedin coordination processor 216 housed within one or more of the cardiactherapy device 210, the external respiratory therapy device 220 orpatient information server 230 in order to develop coordinateddisordered breathing therapy. Control signals generated by thecoordination processor 216 can be sent to other therapy units 212, 222within medical system 200. The control signals developed by coordinationprocessor 216 direct the delivery of coordinated disordered breathingtherapy.

In one implementation, the cardiac therapy and external respiratorytherapy devices 210, 220 may not communicate directly, but maycommunicate indirectly through the APM system 230. In this embodiment,the APM system 230 may operate as an intermediary between two or more ofthe medical devices 210, 220.

FIG. 3 illustrates a block diagram of medical system 300 that may beused to provide coordinated therapies for controlling sleep disorderedbreathing in accordance with an embodiment of the invention. In thisexample, the medical system 300 includes a coordination processor 311disposed within the housing of an implantable cardiac rhythm management(CRM) device 310. The coordination processor 311 utilizes informationrelated to one or more patient conditions to coordinate disorderedbreathing therapies delivered by the external respiration therapy device320 and the CRM device 310. The CRM device 310 may provide additionalmonitoring, diagnostic, and/or therapeutic functions to the patient,including, for example, cardiac pacing and/or defibrillation. Therespiration therapy device 320 may provide additional monitoring,diagnostic and/or therapeutic functions beyond disordered breathingtherapy to the patient.

The CRM device 310 may be electrically coupled to the patient's heartthrough electrodes placed in, on, or about the heart. The cardiacelectrodes may sense cardiac signals produced by the heart and/orprovide therapy to one or more heart chambers. For example, the cardiacelectrodes may deliver electrical stimulation to one or more heartchambers, and/or to one or multiple sites within the heart chambers. TheCRM 310 may directly control delivery of one or more cardiac therapies,such as cardiac pacing, defibrillation, cardioversion, cardiacresynchronization, and/or other cardiac therapies, for example.

The coordination processor 311 disposed within the CRM housing may becoupled to one or more patient internal sensors, patient externalsensors, patient input devices, and/or information systems as describedin connection with FIG. 2. A sensing system may sense various patientconditions associated with the patient's cardiovascular system,respiratory system, cardiopulmonary system, nervous system, musclesystem, and/or other physiological systems. These conditions may be usedto develop a coordinated disordered breathing therapy. The coordinationprocessor 311 may also utilize various environmental or contextualconditions affecting the patient in order to develop a coordinateddisordered breathing therapy.

In the example illustrated in FIG. 3, a medical system 300 comprises apositive airway pressure device 320 used to delivery disorderedbreathing therapy to a patient. Positive airway pressure devices may beused to provide a variety of respiration therapies, including, forexample, continuous positive airway pressure (CPAP), bi-level positiveairway pressure (bi-level PAP), proportional positive airway pressure(PPAP), auto-titrating positive airway pressure, ventilation, gas oroxygen therapies. All types of pressure devices are referred togenerically herein as xPAP devices.

The xPAP device 320 develops a positive air pressure that is deliveredto the patient's airway through tubing 352 and mask 354 connected to thexPAP device 320. Positive airway pressure devices are often used totreat disordered breathing, including central and/or obstructivedisordered breathing types. In one configuration, for example, thepositive airway pressure provided by the xPAP device 320 acts as apneumatic splint keeping the patient's airway open and reducing theseverity and/or number of occurrences of disordered breathing due toairway obstruction.

The coordination processor 311 may utilize one or more patientconditions sensed using sensors and/or input devices as described inconnection with FIG. 2 to coordinate therapy delivered by the xPAPdevice with CRM therapies. Communication circuitry, e.g., communicationcircuitry disposed within the CRM device 310, may be used to transmitthe coordinated disordered breathing therapy information directly to thexPAP device 320 through a wireless communications link, for example.Alternatively, the coordination processor 311 may transfer therapycoordination information to the xPAP 320 device indirectly through anAPM system 330, as described above.

Methodologies involving the use of an implantable medical device todevelop coordinated therapy for sleep disordered breathing are describedin connection with FIG. 3. Although FIG. 3 depicts a coordinationprocessor disposed within a CRM device, other configurations ofcoordination processors and/or therapy devices may alternatively oradditionally be used. For example, other types of external respirationtherapy devices, such as a nebulizer, respirator, ventilator or gastherapy device, may be used to treat sleep disordered breathing. Sleepdisordered breathing therapy devices other than external respiratorytherapy devices may alternatively or additionally be used. For example,the sleep disordered breathing therapy may involve a nerve stimulationtherapy delivered by a nerve stimulation device, a muscle stimulationtherapy delivered by a muscle stimulation device, a drug therapydelivered by a drug pump or other drug delivery device, a cardiacstimulation therapy delivered by a cardiac device, and/or other types ofsleep disordered breathing therapy. Further, the coordination processorneed not be disposed within the housing of a CRM device 310, and maycomprise a stand alone coordination processor. Alternatively, thecoordination processor 311 may be disposed within the housing of therapydevices other than a CRM device 310.

FIG. 4A is a partial view of an implantable device that may includecircuitry for coordinating various therapies for sleep disorderedbreathing in accordance with embodiments of the invention. In thisexample, the coordination processor 435 is configured as a component ofan implantable pulse generator 405 of a cardiac rhythm management (CRM)device 400. The implantable pulse generator 405 is electrically andphysically coupled to an intracardiac lead system 410. The coordinationprocessor 435 may alternatively be implemented in a variety ofimplantable monitoring, diagnostic, and/or therapeutic devices, such asan implantable cardiac monitoring device, an implantable drug deliverydevice, or an implantable neurostimulation device, for example.

Portions of the intracardiac lead system 410 are inserted into thepatient's heart 490. The intracardiac lead system 410 includes one ormore electrodes configured to sense electrical cardiac activity of theheart, deliver electrical stimulation to the heart, sense the patient'stransthoracic impedance, and/or sense other physiological parameters,e.g., cardiac chamber pressure or temperature. Portions of the housing401 of the pulse generator 405 may optionally serve as a can electrode.

Communications circuitry is disposed within the housing 401,facilitating communication between the pulse generator 405 including thecoordination processor 435 and an external device, such as a sleepdisordered breathing therapy device and/or APM system. Thecommunications circuitry can also facilitate unidirectional orbidirectional communication with one or more implanted, external,cutaneous, or subcutaneous physiologic or non-physiologic sensors,patient-input devices and/or information systems.

The pulse generator 405 may optionally incorporate a motion sensor 420.The motion sensor may be configured, for example, to sense patientactivity. Patient activity may be used in connection with sleepdetection as described in more detail herein. The motion sensor 420 maybe implemented as an accelerometer positioned in or on the housing 401of the pulse generator 405. If the motion sensor 420 is implemented asan accelerometer, the motion sensor 420 may also provide acousticinformation, e.g. rales, coughing, S1-S4 heart sounds, cardiac murmurs,and other acoustic information.

The lead system 410 of the CRM device 400 may incorporate atransthoracic impedance sensor that may be used to acquire the patient'srespiration waveform, or other respiration-related information. Thetransthoracic impedance sensor may include, for example, one or moreintracardiac electrodes 441, 442, 451-455, 463 positioned in one or morechambers of the heart 490. The intracardiac electrodes 441, 442,451-455, 463 may be coupled to impedance drive/sense circuitry 430positioned within the housing of the pulse generator 405.

In one implementation, impedance drive/sense circuitry 430 generates acurrent that flows through the tissue between an impedance driveelectrode 451 and a can electrode on the housing 401 of the pulsegenerator 405. The voltage at an impedance sense electrode 452 relativeto the can electrode changes as the patient's transthoracic impedancechanges. The voltage signal developed between the impedance senseelectrode 452 and the can electrode is detected by the impedance sensecircuitry 430. Other locations and/or combinations of impedance senseand drive electrodes are also possible. The impedance signal may also beused to detect other physiological changes besides respiration thatresult in a change in impedance, including pulmonary edema, heart size,cardiac pump function, etc. The respiratory and/or pacemaker therapy maybe altered on the basis of the patient's heart condition as sensed byimpedance.

The voltage signal developed at the impedance sense electrode 452,illustrated in FIG. 7, is proportional to the patient's transthoracicimpedance and represents the patient's respiration waveform. Thetransthoracic impedance increases during respiratory inspiration anddecreases during respiratory expiration. The transthoracic impedance maybe used to determine the amount of air moved in one breath, denoted thetidal volume and/or the amount of air moved per minute, denoted theminute ventilation. A normal “at rest” respiration pattern, e.g., duringnon-REM sleep, includes regular, rhythmic inspiration—expiration cycleswithout substantial interruptions, as indicated in FIG. 7.

Returning to FIG. 4A, the lead system 410 may include one or morecardiac pace/sense electrodes 451-455 positioned in, on, or about one ormore heart chambers for sensing electrical signals from the patient'sheart 490 and/or delivering pacing pulses to the heart 490. Theintracardiac sense/pace electrodes 451-455, such as those illustrated inFIG. 4A, may be used to sense and/or pace one or more chambers of theheart, including the left ventricle, the right ventricle, the leftatrium and/or the right atrium. The lead system 410 may include one ormore defibrillation electrodes 441, 442 for deliveringdefibrillation/cardioversion shocks to the heart.

The pulse generator 405 may include circuitry for detecting cardiacarrhythmias and/or for controlling pacing or defibrillation therapy inthe form of electrical stimulation pulses or shocks delivered to theheart through the lead system 410. The coordination processor 435,including sensor interface circuitry, event detectors, processorcircuitry, and/or memory circuitry, as described in connection with theFIG. 6, may be disposed within the housing 401 of the pulse generator405. The coordination processor 435 may be coupled to various sensors,including the transthoracic impedance sensor 430 and motion sensor 420,patient input devices, and/or information systems through leads orthrough wireless communication links.

The coordination processor 435 may use the information generated by thevarious sensors in order to develop information for coordination ofsleep disordered breathing therapy. In one embodiment, the therapycoordination processor may be positioned outside the pulse generatorhousing 401 and communicatively coupled to the pulse generator 405within generator housing 401, e.g., through a wireless communicationslink.

FIG. 4B is a diagram illustrating an implantable transthoracic cardiacdevice that may be used in connection with developing coordinatedtherapies for sleep disordered breathing in accordance with embodimentsof the invention. The implantable device illustrated in FIG. 4B is animplantable transthoracic cardiac sensing and/or stimulation (ITCS)device that may be implanted under the skin in the chest region of apatient. The ITCS device may, for example, be implanted subcutaneouslysuch that all or selected elements of the device are positioned on thepatient's front, back, side, or other body locations suitable forsensing cardiac activity and delivering cardiac stimulation therapy. Itis understood that elements of the ITCS device may be located at severaldifferent body locations, such as in the chest, abdominal, or subclavianregion with electrode elements respectively positioned at differentregions near, around, in, or on the heart.

Circuitry for implementing a disordered breathing therapy coordinationprocessor may be positioned within the primary housing of the ITCSdevice. The primary housing (e.g., the active or non-active can) of theITCS device, for example, may be configured for positioning outside ofthe rib cage at an intercostal or subcostal location, within theabdomen, or in the upper chest region (e.g., subclavian location, suchas above the third rib). In one implementation, one or more electrodesmay be located on the primary housing and/or at other locations about,but not in direct contact with the heart, great vessel or coronaryvasculature.

In another implementation, one or more electrodes may be located indirect contact with the heart, great vessel or coronary vasculature,such as via one or more leads implanted by use of conventionaltransvenous delivery approaches. In another implementation, for example,one or more subcutaneous electrode subsystems or electrode arrays may beused to sense cardiac activity and deliver cardiac stimulation energy inan ITCS device configuration employing an active can or a configurationemploying a non-active can. Electrodes may be situated at anteriorand/or posterior locations relative to the heart.

In the configuration shown in FIG. 4B, a subcutaneous electrode assembly407 can be positioned under the skin in the chest region and situateddistal from the housing 402. The subcutaneous and, if applicable,housing electrode(s) can be positioned about the heart at variouslocations and orientations, such as at various anterior and/or posteriorlocations relative to the heart. The subcutaneous electrode assembly 407is coupled to circuitry within the housing 402 via a lead assembly 406.One or more conductors (e.g., coils or cables) are provided within thelead assembly 406 and electrically couple the subcutaneous electrodeassembly 407 with circuitry in the housing 402. One or more sense,sense/pace or defibrillation electrodes can be situated on the elongatedstructure of the electrode support, the housing 402, and/or the distalelectrode assembly (shown as subcutaneous electrode assembly 407 in FIG.4B).

It is noted that the electrode and the lead assemblies 407, 406 can beconfigured to assume a variety of shapes. For example, the lead assembly406 can have a wedge, chevron, flattened oval, or a ribbon shape, andthe subcutaneous electrode assembly 407 can comprise a number of spacedelectrodes, such as an array or band of electrodes. Moreover, two ormore subcutaneous electrode assemblies 407 can be mounted to multipleelectrode support assemblies 406 to achieve a desired spacedrelationship amongst subcutaneous electrode assemblies 407.

In particular configurations, the ITCS device may perform functionstraditionally performed by cardiac rhythm management devices, such asproviding various cardiac monitoring, pacing and/orcardioversion/defibrillation functions. Exemplary pacemaker circuitry,structures and functionality, aspects of which can be incorporated in anITCS device of a type that may benefit from multi-parameter sensingconfigurations, are disclosed in commonly owned U.S. Pat. Nos.4,562,841; 5,284,136; 5,376,476; 5,036,849; 5,540,727; 5,836,987;6,044,298; and 6,055,454, which are hereby incorporated herein byreference in their respective entireties. It is understood that ITCSdevice configurations can provide for non-physiologic pacing support inaddition to, or to the exclusion of, bradycardia and/or anti-tachycardiapacing therapies. Exemplary cardiac monitoring circuitry, structures andfunctionality, aspects of which can be incorporated in an ITCS of thepresent invention, are disclosed in commonly owned U.S. Pat. Nos.5,313,953; 5,388,578; and 5,411,031, which are hereby incorporatedherein by reference in their respective entireties.

An ITCS device can incorporate circuitry, structures and functionalityof the subcutaneous implantable medical devices disclosed in commonlyowned U.S. Pat. Nos. 5,203,348; 5,230,337; 5,360,442; 5,366,496;5,397,342; 5,391,200; 5,545,202; 5,603,732; and 5,916,243 and commonlyowned U.S. Patent Application Ser. No. 60/462,272, filed Apr. 11, 2003,Ser. No. 10/462,001, filed Jun. 13, 2003, Ser. No. 10/465,520, filedJun. 19, 2003, Ser. No. 10/820,642 filed Apr. 8, 2004 and Ser. No.10/821,248, filed Apr. 8, 2004 which are incorporated herein byreference.

The housing of the ITCS device may incorporate components of acoordination processor 409. The coordination processor 409 may becoupled to one or more sensors, patient input devices, and/orinformation systems as described in connection with FIG. 2.

In one implementation, the ITCS device may include an impedance sensorconfigured to sense the patient's transthoracic impedance. The impedancesensor may include the impedance drive/sense circuitry incorporated withthe housing 402 of the ITCS device and coupled to impedance electrodespositioned on the can or at other locations of the ITCS device, such ason the subcutaneous electrode assembly 407 and/or lead assembly 406. Inone configuration, the impedance drive circuitry generates a currentthat flows between a subcutaneous impedance drive electrode and a canelectrode on the primary housing of the ITCS device. The voltage at asubcutaneous impedance sense electrode relative to the can electrodechanges as the patient's transthoracic impedance changes. The voltagesignal developed between the impedance sense electrode and the canelectrode is sensed by the impedance drive/sense circuitry.

Communications circuitry is disposed within the housing 402 forfacilitating communication between the ITCS device, including thecoordination processor 409, and an external therapy device, e.g.,external respiratory therapy device, or other device such as a portableor bed-side communication station, patient-carried/worn communicationstation, or external programmer, for example. The communicationscircuitry can also facilitate unidirectional or bidirectionalcommunication with one or more external, cutaneous, or subcutaneousphysiologic or non-physiologic sensors.

FIG. 5 illustrates a block diagram of a sleep disordered breathingtherapy device 500, e.g., xPAP device that may be used to providetherapy in accordance with embodiments of the invention. An implantabletherapy coordination device, implemented as a component of the CRM orITCS systems described in connection with FIGS. 4A and 4B, respectively,may collect information used for coordinating sleep disordered breathingtherapy. Other types of sleep disordered breathing therapy devices mayalternatively or additionally be employed within the context of thepresent invention. For example, sleep disordered breathing therapy maybe provided by a muscle stimulation device, a nerve stimulation device,a drug delivery device, and/or other devices that can be used incoordination to treat sleep disordered breathing.

As previously discussed, the xPAP device 500 may include any of thepositive airway pressure devices, including CPAP, bi-level positiveairway pressure (bi-PAP), proportional positive airway pressure (PPAP),and/or autotitration positive airway pressure devices, for example.Continuous positive airway pressure (CPAP) devices deliver a set airpressure to the patient. The pressure level for the individual patientmay be determined during a titration study. Such a study may take placein a sleep lab, and involves determination of the optimum airwaypressure by a sleep physician or other professional. The CPAP devicepressure control is set to the determined level. When the patient usesthe CPAP device, a substantially constant airway pressure level ismaintained by the device.

Autotitration PAP devices are similar to CPAP devices, however, thepressure controller for autotitration devices automatically determinesthe air pressure for the patient. Instead of maintaining a constantpressure, the autotitration PAP device evaluates sensor signals and thechanging needs of the patient to deliver a variable positive airwaypressure. Autotitration PAP and CPAP are often used to treat sleepdisordered breathing, for example.

Bi-level positive airway pressure (bi-PAP) devices provide two levels ofpositive airway pressure. A higher pressure is maintained while thepatient inhales. The device switches to a lower pressure duringexpiration. Bi-PAP devices are used to treat a variety of respiratorydysfunctions, including chronic obstructive pulmonary disease (COPD),respiratory insufficiency, and ALS or Lou Gehrig's disease, amongothers.

Sleep disordered breathing therapy may be provided by a servoventilation device. Servo ventilation devices provide airway pressuredependent on the respiration cycle stage. A servo ventilation deviceprovides positive pressure on inhalation and negative pressure onexhalation.

The breathing therapy control unit 540 includes a flow generator 542that pulls in air through a filter. The flow generator 542 is controlledby the pressure control circuitry 544 to deliver an appropriate airpressure to the patient. Air flows through tubing 546 coupled to thexPAP device 500 and is delivered to the patient's airway through a mask548. In one example, the mask 548 may be a nasal mask covering only thepatient's nose. In another example, the mask 548 covers the patient'snose and mouth.

The xPAP device 500 may include a communications unit 580 forcommunicating with one or more separate devices, includingpatient-external and/or patient-internal monitoring, diagnostic and/ortherapeutic devices 590. In one example, the xPAP device 500 may receivetherapy coordination information from a coordination processor disposedwithin an implantable monitoring and/or therapy device. In anotherexample, the xPAP device 500 may receive therapy coordinationinformation from a patient management server or other computing devicecoupled to the medical device.

The block diagram of FIG. 6 illustrates an example of system 600including a fully or partially implantable device 601 that may be usedto monitor patient conditions and to coordinate sleep disorderedbreathing therapy in accordance with embodiments of the invention. Themedical device 601 may be coupled to an array of data acquisitiondevices, including patient-internal sensors 611, patient-externalsensors 612, patient input devices 613, and/or other information systems614 as described in more detail above.

Patient conditions monitored by the implantable device 601 may includeboth physiological and non-physiological contextual conditions affectingthe patient. Physiological conditions may include a broad category ofconditions associated with the internal functioning of the patient'sphysiological systems, including the cardiovascular, respiratory,nervous, muscle and other systems. Examples of physiological conditionsinclude blood chemistry, patient posture, patient activity, respirationquality, sleep quality, among others.

Contextual conditions are non-physiological conditions representingpatient-external or background conditions. Contextual conditions may bebroadly defined to include, for example, present environmentalconditions, such as patient location, ambient temperature, humidity, airpollution index. Contextual conditions may also includehistorical/background conditions relating to the patient, including thepatient's normal sleep time and the patient's medical history, forexample. Methods and systems for detecting some contextual conditions,including, for example, proximity to bed detection, are described incommonly owned U.S. patent application Ser. No. 10/269,611, filed Oct.11, 2002, which is incorporated herein by reference.

Table 1 provides a representative set of patient conditions that may bemonitored by the device 601 in accordance with embodiments of theinvention. Table 1 also provides illustrative sensing methods that maybe employed to sense the conditions. It will be appreciated that patientconditions and detection methods other than those listed in Table 1 maybe used and are considered to be within the scope of the invention.

TABLE 1 Sensor type or Condition Type Condition Detection methodPhysiological Cardiovascular Heart rate EGM, ECG System Heart ratevariability QT interval Ventricular filling Intracardiac pressurepressure sensor Blood pressure Blood pressure sensor Respiratory SnoringAccelerometer System Microphone Respiration pattern Transthoracic (Tidalvolume impedance sensor Minute ventilation (AC) Respiratory rate)Patency of upper Intrathoracic airway impedance sensor PulmonaryTransthoracic congestion impedance sensor (DC) Nervous Sympathetic nerveMuscle sympathetic System activity nerve Activity sensor Brain activityEEG Blood CO2 saturation Blood analysis Chemistry O2 saturation Bloodalcohol content Adrenalin Brain Natriuretic Peptide (BNP) C-ReactiveProtein Drug/Medication/ Tobacco use Muscle Muscle atonia EMG System Eyemovement EOG Patient activity Accelerometer, MV, etc. Limb movementsAccelerometer, EMG Jaw movements Accelerometer, EMG Posture Multi-axisaccelerometer Contextual Environmental Ambient Thermometer temperatureHumidity Hygrometer Pollution Air quality website Time Clock Barometricpressure Barometer Ambient noise Microphone Ambient light PhotodetectorAltitude Altimeter Location GPS, proximity sensor Proximity to bedProximity to bed sensor Historical/ Historical sleep Patient input,Background time previously detected sleep onset times Medical historyPatient input Age Recent exercise Weight Gender Body mass index Necksize Emotional state Psychological history Daytime sleepiness Patientperception of sleep quality Drug, alcohol, nicotine use

The implantable device 601 of FIG. 6 includes a coordination processor637 for processing signals received from the sensors, 611, 612, patientinput devices 613, and/or other information system 614. The coordinationprocessor 637 may include one or more a detection units 624, 626, 628that detect the occurrence of various physiological events. For example,the coordination processor 637 may include one or more of a disorderedbreathing detector 624, a sleep detector 628, and/or a therapy usagedetector 626. Other event detection components may also be included. Thecoordination processor 637 may be used to calculate various indices,e.g., AHI, % PB, and/or arousals per unit time, used for evaluatingtherapy efficacy, and/or therapy impact. The coordination processor 637may compare the patient's therapy usage to a prescribed therapy todetermine therapy compliance. The coordination processor 637 can developcontrol signals for implementing a coordinated therapy based on themonitored conditions, the detected events, and/or the calculatedindices.

In one exemplary implementation, the disordered breathing detector 624may be coupled to a respiration sensor. The disordered breathingdetector 624 may use the respiration signal developed by the respirationsensor to detect disordered breathing events based on the inspiratoryand expiratory phases of the patient's respiration cycles, for example.The sleep detector 628 may analyze various inputs from thepatient-internal sensors 611, patient-external sensors 612, patientinput devices 613, other information systems 614 to detect sleep-relatedevents, including, for example, sleep onset, sleep offset, sleep stages,and arousals from sleep.

The coordination processor 637 may include a memory 636 for storinginformation derived from signals produced by the patient-internalsensors 611, patient-external sensors 612, patient input devices 613,and/or other information systems 614. The memory 636 may also storeinformation about detected events, e.g., sleep and disordered breathingevents, and/or information related to calculated indices characterizingvarious events such as sleep and/or disordered breathing events. Thestored data may be used by coordination processor 637 to develop acoordinated disordered breathing therapy. The stored data may beretrieved by another component of the medical device 601 for later use,or may be transmitted to a separate device 640 for storage, furtherprocessing, trending, analysis and/or display, for example. In onescenario, the stored data can be downloaded to a separate deviceperiodically or on command. The stored data may be presented to thepatient's health care professional on a real-time basis, or as along-term, e.g., month long or year long, trend of daily measurements.

In the particular embodiment illustrated in FIG. 6, the medical device601 includes a cardiac therapy unit 675. This example, the medicaldevice 601 comprises a cardiac therapy device 675 configured as acardiac pulse generator to deliver cardiac electrical stimulationtherapy via electrical stimulation electrodes 652.

The medical device 601 may further include a communications unit 606that controls communications between the medical device 601 and otherdevices or systems. For example, the communications unit 606 may be usedto provide wireless or wired communications links between the medicaldevice 601 and one or more of the patient-internal sensors 611,patient-external sensors 612, patient input devices 613, and informationsystems 614.

The communications unit 606 may also facilitate communications betweenthe medical device 601 and a remote device 640 such as another sleepdisordered breathing therapy device, a programmer, and/or an APM system.The wireless connections coupling the medical device 601 to variousother devices and systems may utilize a variety of wireless protocols,including, for example, Bluetooth, IEEE 802.11, and/or a proprietarywireless protocol.

Detecting the onset, termination, duration, stages, and quality of sleepexperienced by a patient may be employed in connection with constructinga coordinated disordered breathing therapy. Patients suffering fromsleep apnea, or other types of sleep disordered breathing, may betreated for sleep disordered breathing only during periods of sleep.Coordinating disordered breathing therapy may involve determining if thepatient is asleep and/or detecting various sleep-related processes, suchas arousals from sleep and/or REM or non-REM sleep stages.

In addition, information associated with patient sleep may be used toassess an impact of breathing therapy on the patient. Therapy impactdata may be used to develop information to coordinate and adjust thetherapy. The implantable monitoring device 601 may include a sleepdetector 628 for detecting when the patient is asleep and various stagesand/or processes of sleep. Various methods of sleep detectionimplementable in an implanted device involve sensing one or moreconditions indicative of sleep. The sleep-related conditions may becompared to one or more thresholds to determine if the patient isasleep.

The sleep-related conditions may be sensed or derived usingpatient-external or implantable sensors and analyzed by a sleep detectorcoupled to or incorporated in the implantable therapy coordinationdevice. For example, sleep detection may be implemented in animplantable cardiac rhythm management system configured as apacemaker/defibrillator and incorporating a coordination processor asillustrated in FIG. 4A or the ITCS device illustrated in FIG. 4B.

Sleep detection may involve sensing one or more conditions indicative ofsleep. A representative set of sleep-related conditions include bodymovement, heart rate, QT interval, eye movement, respiration rate,transthoracic impedance, tidal volume, minute ventilation, body posture,brain activity, cardiac activity, muscle tone, body temperature, time ofday, historical sleep times, blood pressure, and blood gasconcentration, proximity to bed, for example.

Sleep may be detected by comparing levels of the one or moresleep-related conditions to one or more sleep thresholds. For example,sleep may be detected by monitoring the patient's heart rate. When thepatient's heart rate decreases below a sleep threshold, the patient maybe determined to be asleep. Sleep may also be detected by monitoring thepatient's activity. If the patient's activity decreases below a sleepthreshold, then the patient may be determined to be asleep. Anothermethod of detecting sleep involves monitoring the patient's minuteventilation. If the patient's minute ventilation falls below a sleepthreshold, then the patient may be determined to be asleep.

Sleep may be detected by comparing multiple sleep-related conditions tomultiple thresholds. For example, the patient may be determined to beasleep if the patient's activity, sensed by an accelerometer, fallsbelow an activity sleep threshold and the patient's heart rate, sensedby cardiac electrodes, falls below a heart rate sleep threshold.

Sleep may also be detected using one sleep-related condition to modifythe sleep threshold of another sleep-related condition. A firstsleep-related condition may be sensed. The level of the sleep-relatedcondition may be compared to a sleep threshold to determine the onsetand termination of sleep. A second sleep-related condition may be usedto adjust the sleep threshold. Additional sleep-related conditions mayoptionally be sensed to confirm the onset or termination of the sleepcondition.

A sleep detector 628 (FIG. 6) may be configured to compare the levels ofone or more sleep-related conditions to one or more thresholds. In oneimplementation, the one sleep related condition may be compared to asleep threshold or other index to detect sleep. In anotherimplementation, multiple sleep-related conditions may be compared tomultiple thresholds or indices. In a further implementation, one or moreof the sleep-related conditions may be used to adjust the sleepthresholds or indices. Furthermore, the onset or termination of sleepmay be confirmed using an additional number of sleep-related conditions.

The sleep-related conditions may be sensed using implantable sensorsand/or patient-external sensors, for example. In one embodiment, patientactivity may be compared to a sleep threshold to determine when thepatient is asleep. A low level of activity is indicative that thepatient is sleeping. Patient activity may be sensed, for example, usingan accelerometer positioned on or in the housing of an implantablecardiac device, or in another convenient location. The accelerometersignal may be correlated with activity level or workload.

A second sleep-related condition may be used to adjust the sleepthreshold. In one embodiment, the patient's minute ventilation is usedto adjust the sleep threshold. The patient's respiration may be sensedusing a transthoracic impedance sensor. Transthoracic impedance may beused to derive various parameters associated with respiration,including, for example, tidal volume and/or minute ventilation. Atransthoracic impedance sensor may be integrated into an implantablecardiac device with intracardiac electrodes, for example. Impedancedriver circuitry generates a current that flows through the bloodbetween the impedance drive electrode and a can electrode on the housingof the cardiac device. The voltage at an impedance sense electroderelative to the can electrode changes as the transthoracic impedancechanges.

The voltage signal developed at the impedance sense electrode,illustrated in FIG. 7, is proportional to the transthoracic impedance,with the impedance increasing during respiratory inspiration anddecreasing during respiratory expiration. The peak-to-peak transition ofthe impedance, illustrated in FIG. 7, is proportional to the amount ofair inhaled in one breath, denoted the tidal volume. The variations inimpedance during respiration may be used to determine the respirationtidal volume, corresponding to the volume of air moved in a breath, orminute ventilation corresponding to the amount of air moved per minute.

FIG. 8 is a flowchart illustrating a method of detecting sleep accordingto an embodiment of the invention. A sleep threshold associated with afirst sleep-related condition is established. The sleep threshold may bedetermined from clinical data of a sleep threshold associated with sleepacquired using a group of subjects, for example. The sleep threshold mayalso be determined using historical data taken from the particularpatient for whom onset and offset of sleep is to be determined. Forexample, a history of a particular patient's sleep times can be stored,and a sleep threshold can be developed using data associated with thepatient's sleep time history.

First and second signals associated with sleep-related conditions aresensed 810, 820. The first and the second signals may be any signalassociated with the condition of sleep, such as the representativesleep-related conditions associated with sleep listed above.

The sleep threshold established for the first signal is adjusted 830using the second signal. For example, if the second signal indicatescondition, e.g., high level of patient activity that is incompatiblewith a sleep state, the sleep threshold of the first signal may beadjusted downward to require sensing a decreased level of the firstsignal before a sleep condition is detected.

If the first signal is consistent with sleep according to the adjustedsleep threshold 840, a sleep condition is detected 850. If the firstsignal is not consistent with sleep using the adjusted sleep threshold,the first and the second signals continue to be sensed 810, 820 and thethreshold adjusted 830 until a condition of sleep is detected 850.

In another embodiment of the invention, illustrated in the flowchart ofFIG. 9, an accelerometer and a minute ventilation sensor are used todevelop the first and second signals associated with sleep. Apreliminary accelerometer signal sleep threshold is determined 910. Forexample, the preliminary sleep threshold may be determined from clinicaldata taken from a group of subjects or historical data taken from thepatient over a period of time.

The activity level of the patient is monitored using an accelerometer920 that may be incorporated into an implantable cardiac pacemaker asdescribed above. Alternatively, the accelerometer may be attachedexternally to the patient. The patient's minute ventilation (MV) signalis monitored 925. The MV signal may be acquired, for example, based onthe transthoracic impedance signal as described above using animplantable cardiac device. Other methods of determining the MV signalare also possible and are considered to be within the scope of thisinvention.

In this example, the accelerometer signal represents the sleep detectionsignal that is compared to the sleep threshold. The MV signal is thethreshold adjustment signal used to adjust the sleep threshold. Heartrate is monitored 930 in this example to provide a sleep confirmationsignal.

Threshold adjustment may be accomplished by using the patient's MVsignal to moderate the accelerometer sleep threshold. If the patient'sMV signal is low relative to an expected MV level associated with sleep,the accelerometer sleep threshold is increased. Similarly, if thepatient's MV signal level is high relative to an expected MV levelassociated with sleep, the accelerometer sleep threshold is decreased.Thus, when the patient's MV level is high, less activity is required tomake the determination that the patient is sleeping. Conversely when thepatient's MV level is relatively low, a higher activity level may resultin detection of sleep. The use of two sleep-related signals to determinea sleep condition enhances the accuracy of sleep detection over previousmethods using only one sleep-related signal to determine that a patientis sleeping.

Various signal processing techniques may be employed to process the rawsensor signals. For example, a moving average of a plurality of samplesof each sleep-related signal may be calculated and used as thesleep-related signal. Furthermore, the sleep-related signals may befiltered and/or digitized. If the MV signal is high 935 relative to anexpected MV level associated with sleep, the accelerometer sleepthreshold is decreased 940. If the MV signal is low 935 relative to anexpected MV level associated with sleep, the accelerometer sleepthreshold is increased 945.

If the sensed accelerometer signal is less than or equal to the adjustedsleep threshold 950, and if the patient is not currently in a sleepstate 965, then the patient's heart rate is checked 980 to confirm thesleep condition. If the patient's heart rate is compatible with sleep980, then sleep onset is determined 990. If the patient's heart rate isincompatible with sleep, then the patient's sleep-related signalscontinue to be monitored.

If the accelerometer signal is less than or equal to the adjusted sleepthreshold 950 and if the patient is currently in a sleep state 965, thena continuing sleep state is determined 975 and the patient'ssleep-related signals continue to be monitored for sleep termination tooccur.

If the accelerometer signal is greater than the adjusted sleep threshold950 and the patient is not currently in a sleep state 960, then thepatient's sleep-related signals continue to be monitored until sleeponset is detected 990. If the accelerometer signal is greater than theadjusted sleep threshold 950 and the patient is currently in a sleepstate 960, then sleep termination is detected 970.

The graphs of FIGS. 10-12 illustrate the adjustment of the accelerometersleep threshold using the MV signal. The relationship between patientactivity and the accelerometer and MV signals is trended over a periodof time to determine relative signal levels associated with a sleepcondition. FIG. 10A illustrates activity as indicated by theaccelerometer signal. The patient's heart rate for the same period isgraphed in FIG. 10B. The accelerometer signal indicates a period ofsleep associated with a relatively low level of activity beginning atslightly before 23:00 and continuing through 6:00. Heart rateappropriately tracks the activity level indicated by the accelerometerindicating a similar period of low heart rate corresponding to sleep.The accelerometer trends are used to establish a threshold for sleepdetection.

FIG. 11 is a graph of baseline trending for an MV signal. Historicaldata of minute ventilation of a patient is graphed over an 8 monthperiod. The MV signal trending data is used to determine the MV signallevel associated with sleep. In this example, a composite MV signalusing the historical data indicates a roughly sinusoidal shape with therelatively low MV levels occurring approximately during the period fromhours 21:00 through 8:00. The low MV levels are associated with periodsof sleep. The MV signal level associated with sleep is used to implementsleep threshold adjustment.

FIG. 12 illustrates adjustment of the accelerometer sleep thresholdusing the MV signal. The initial sleep threshold 1210 is establishedusing the baseline accelerometer signal data acquired as discussedabove. If the patient's MV signal is low relative to an expected MVlevel associated with sleep, the accelerometer sleep threshold isincreased 1220. If the patient's MV signal level is high relative to anexpected MV level associated with sleep, the accelerometer sleepthreshold is decreased 1230. When the patient's MV level is high, lessactivity detected by the accelerometer is required to make thedetermination that the patient is sleeping. However, if the patient's MVlevel is relatively low a higher activity level may result in detectionof sleep. The use of two sleep-related signals to adjust a sleepthreshold for determining a sleep condition enhances the accuracy ofsleep detection over previous methods.

Additional sleep-related signals may be sensed and used to improve thesleep detection mechanism described above. For example, a posture sensormay be used to detect the posture of the patient and used to confirmsleep. If the posture sensor indicates a vertical posture, then theposture sensor signal may be used to override a determination of sleepusing the sleep detection and threshold adjustment signals. Othersignals may also be used in connection with sleep determination orconfirmation, including the representative set of sleep-related signalsassociated with sleep indicated above. Methods and systems related tosleep detection, aspects of which may be utilized in connection with themethodologies of the present invention, are described in commonly ownedU.S. patent application Ser. No. 10/309,771, filed Dec. 4, 2002 andincorporated herein by reference.

The above described sleep-detection methods may be used fordiscriminating between periods of sleep and periods of wakefulness.Knowledge of sleep onset, offset, arousal episodes, and/or length ofuninterrupted sleep may provide useful information for coordinatingsleep disordered breathing therapy and/or be used to monitor patientconditions.

Sleep stage discrimination, including REM and non-REM sleep stages mayadditionally be used in connection with disordered breathing therapy.For example, some patients may experience sleep disordered breathingprimarily during particular sleep stages. The implantable device maymonitor sleep stages and disordered breathing episodes. The disorderedbreathing information may be analyzed in view of the sleep stageinformation. The analysis may be helpful in adapting a breathing therapyfor a patient, e.g. delivering breathing therapy during sleep stagesthat predispose the patient to disordered breathing episodes. In oneimplementation, sleep information associated with sleep stages and/orarousals from sleep may be determined using information from an EEGsensor.

In another implementation, sleep stage information may be obtained usingone or more muscle atonia sensors. Methods and systems for implementingof sleep stage detection using muscle atonia sensors are described incommonly owned U.S. patent application Ser. No. 10/643,006, filed onAug. 18, 2003, which is incorporated herein by reference.

Various aspects of sleep quality, including number and severity ofarousals, sleep disordered breathing episodes, limb movements duringsleep, and cardiac, respiratory, muscle, and nervous system functioningduring sleep may provide important information relevant to the deliveryof coordinated breathing therapy. Methods and systems for collecting andassessing sleep quality data are described in commonly owned U.S. patentapplication Ser. No. 10/642,998, filed Aug. 18, 2003, which isincorporated herein by reference.

Determining the effectiveness and/or impact of coordinated sleepdisordered breathing therapy may involve detecting the sleep disorderedbreathing episodes. Sleep disordered breathing is a serious respiratorycondition involving disruption of the normal respiratory cycle. Therespiratory disruptions caused by disordered breathing can beparticularly serious for patients concurrently suffering fromcardiovascular deficiencies, such as congestive heart failure.Unfortunately, disordered breathing is often undiagnosed. If leftuntreated, the effects of disordered breathing may result in serioushealth consequences for the patient.

Episodes of disordered breathing are associated with acute and chronicphysiological effects. Acute responses to disordered breathing mayinclude, for example, negative intrathoracic pressure, hypoxia, arousalfrom sleep, and increases in blood pressure and heart rate. Duringobstructive apnea episodes, negative intrathoracic pressure may arisefrom an increased effort to generate airflow. Attempted inspiration inthe presence of an occluded airway results in an abrupt reduction inintrathoracic pressure. The repeated futile inspiratory effortsassociated with obstructive sleep apnea may trigger a series ofsecondary responses, including mechanical, hemodynamic, chemical,neural, and inflammatory responses.

Obstructive sleep apneas may be terminated by arousal from sleep severalseconds after the apneic peak, allowing the resumption of airflow.Coincident with arousal from sleep, surges in sympathetic nerveactivity, blood pressure, and heart rate may occur. The adverse effectsof obstructive apnea are not confined to sleep. Daytime sympatheticnerve activity and systemic blood pressure are increased. There may alsobe a sustained reduction in vagal tone, causing reduction in total heartrate variability during periods of wakefulness.

Central sleep apnea is generally caused by a failure of respiratorycontrol signals from the brain. Central sleep apnea is a component ofCheyne-Stokes respiration (CSR), a respiration pattern primarilyobserved in patients suffering from chronic heart failure (CHF).Cheyne-Stokes respiration is a form of periodic breathing in whichcentral apneas and hypopneas alternate with periods of hyperventilationcausing a waxing-waning pattern of tidal volume. In some CHF patients,obstructive sleep apnea and central sleep apnea may coexist. In thesepatients, there may be a gradual shift from predominantly obstructiveapneas at the beginning of the night to predominantly central apneas atthe end of the night.

Disordered breathing may be detected by sensing and analyzing variousconditions associated with disordered breathing. Table 2 providesexamples of how a representative subset of the physiological andcontextual conditions listed in Table 1 may be used in connection withdisordered breathing detection.

Detection of disordered breathing may involve comparing one condition ormultiple conditions to one or more thresholds or other indicesindicative of disordered breathing. A threshold or other indexindicative of disordered breathing may comprise a predetermined level ofa particular condition, e.g., blood oxygen level less than apredetermined amount. A threshold or other index indicative ofdisordered breathing may comprises a change in a level of a particularcondition, e.g., heart rate decreasing from a sleep rate to lower ratewithin a predetermined time interval.

In one approach, the relationships between the conditions may beindicative of disordered breathing. In this embodiment, disorderedbreathing detection may be based on the existence and relative valuesassociated with two or more conditions. For example, if condition A ispresent at a level of x, then condition B must also be present at alevel of f(x) before a disordered breathing detection is made.

The thresholds and/or relationships indicative of disordered breathingmay be highly patient specific. The thresholds and/or relationshipsindicative of disordered breathing may be determined on a case-by-casebasis by monitoring conditions affecting the patient and monitoringdisordered breathing episodes. The analysis may involve determininglevels of the monitored conditions and/or relationships between themonitored conditions associated, e.g., statistically correlated, withdisordered breathing episodes. The thresholds and/or relationships usedin disordered breathing detection may be updated periodically to trackchanges in the patient's response to disordered breathing.

TABLE 2 Condition Examples of how condition may be used in TypeCondition disordered breathing detection Physio- Heart rate Decrease inheart rate may indicate disordered logical breathing episode. Increasein heart rate may indicate autonomic arousal from a disordered breathingepisode. Decrease in heart rate may indicate the patient is asleep.Heart rate Disordered breathing causes heart rate variabilityvariability to decrease. Changes in HRV associated with sleep disorderedbreathing may be observed while the patient is awake or asleepVentricular May be used to identify/predict pulmonary filling congestionassociated with respiratory pressure disturbance. Blood Swings inon-line blood pressure measures are pressure associated with apnea.Disordered breathing generally increases blood pressure variability -these changes may be observed while the patient is awake or asleep.Snoring Snoring is associated with a higher incidence of obstructivesleep apnea and may be used to detect disordered breathing. RespirationRespiration patterns including, e.g., respiration pattern/rate rate, maybe used to detect disordered breathing episodes. Respiration patternsmay be used to determine the type of disordered breathing. Respirationpatterns may be used to detect that the patient is asleep. Patency ofPatency of upper airway is related to upper obstructive sleep apnea andmay be used to airway detect episodes of obstructive sleep apnea.Pulmonary Pulmonary congestion is associated with congestion respiratorydisturbances. Sympathetic End of apnea associated with a spike in SNA.nerve Changes in SNA observed while the patient is activity awake orasleep may be associated with sleep disordered breathing CO2 Low CO2levels initiate central apnea. O2 O2 desaturation occurs during severeapnea/hypopnea episodes. Blood Alcohol tends to increase incidence ofsnoring alcohol & obstructive apnea. content Adrenalin End of apneaassociated with a spike in blood adrenaline. BNP A marker of heartfailure status, which is associated with Cheyne-Stokes RespirationC-Reactive A measure of inflammation that may be related Protein toapnea. Drug/ These substances may affect the incidence of Medication/both central & obstructive apnea. Tobacco use Muscle Muscle atonia maybe used to detect REM and atonia non-REM sleep. Eye Eye movement may beused to detect REM movement and non-REM sleep. Contextual TemperatureAmbient temperature may be a condition predisposing the patient toepisodes of disordered breathing and may be useful in disorderedbreathing detection. Humidity Humidity may be a condition predisposingthe patient to episodes of disordered breathing and may be useful indisordered breathing detection. Pollution Pollution may be a conditionpredisposing the patient to episodes of disordered breathing and may beuseful in disordered breathing detection. Posture Posture may be used toconfirm or determine the patient is asleep. Activity Patient activitymay be used in relation to sleep detection. Location Patient locationmay used to determine if the patient is in bed as a part of sleepdetection. Altitude Lower oxygen concentrations at higher altitudestends to cause more central apnea

In various implementations, episodes of disordered breathing may bedetected and classified by analyzing the patient's respiration patterns.Methods and systems of disordered breathing detection based onrespiration patterns are further described in commonly owned U.S. patentapplication Ser. No. 10/309,770, filed Dec. 4, 2002, which isincorporated herein by reference.

Once disordered breathing is identified based on the sensed conditionsindicative of disordered breathing, delivery of therapy can becoordinated based on the detected disordered breathing.

Similar to detecting disordered breathing, predicting disorderedbreathing based on sensed conditions is patient specific. Each of theconditions listed in Table 1 may serve a variety of purposes inpredicting disordered breathing. Various subsets of the conditionslisted in Table 1 may be detected as predisposing conditions, precursorconditions, and/or verification conditions useful in the prediction ofdisordered breathing. In one example, information regarding sleep onsetmay be employed in prediction of sleep disordered breathing. A subset ofthe conditions listed in Table 1 may be used to detect whether thepatient is asleep and to track the various stages of sleep. Anothersubset of the conditions may be employed to detect and classifydisordered breathing episodes. Table 3 below provides further examplesof how the physiological and contextual conditions of the patient may beused in disordered breathing prediction.

TABLE 3 Examples of how condition is used in disordered Conditionbreathing prediction Heart rate Decrease in heart rate may indicatedisordered breathing episode. Decrease in heart rate may indicate thepatient is asleep. Increase in heart rate may indicate autonomic arousalfrom disordered breathing. Heart rate May be used to determine sleepstate variability Ventricular May be used to identify/predict pulmonarycongestion filling pressure associated with respiratory disturbance.Blood pressure Swings in on-line blood pressure measures are associatedwith apnea. Snoring Snoring is associated with a higher incidence ofobstructive sleep apnea and may be used to detect disordered breathing.Respiration Respiration patterns may be used to detectsignals/respiration disordered breathing episodes. patterns Respirationpatterns may be used to determine the type of disordered breathing.Respiration patterns may be used to detect that the patient is asleep.Hyperventilation may be used to predict disordered breathing. Previousepisodes of disordered breathing may be used to predict furtherepisodes. One form of disordered breathing may be used to predictanother form of disordered breathing Patency Patency of upper airway isrelated to obstructive of upper sleep apnea and may be used to detectepisodes of airway obstructive sleep apnea. Pulmonary Pulmonarycongestion is associated with respiratory congestion disturbances.Sympathetic End of apnea associated with a spike in SNA nerve activityCO2 saturation Low CO2 levels initiate central apnea. O2 saturation O2desaturation occurs during severe apnea/hypopnea episodes. Blood Alcoholtends to increase incidence of snoring & alcohol obstructive apnea.content Adrenalin End of apnea associated with a spike in bloodadrenaline. BNP A marker of heart failure status, which is associatedwith Cheyne-Stokes Respiration C-Reactive A measure of inflammation thatmay be related to Protein apnea. Drug/ These substances may affectincidence of both Medication/ central & obstructive apnea. Tobacco useMuscle Muscle atonia may be used to detect REM and non- atonia REMsleep. Eye Eye movement may be used to detect REM and non- movement REMsleep. Temperature Ambient temperature may be a condition predisposingthe patient to episodes of disordered breathing. Humidity Humidity maybe a condition predisposing the patient to episodes of disorderedbreathing. Pollution Pollution may be a condition predisposing thepatient to episodes of disordered breathing. Posture Posture may be usedto determine if the patient is asleep. Posture may be a conditionpredisposing the patient to episodes of disordered breathing. ActivityPatient activity may be used in relation to sleep detection. Sleep stageNREM sleep is associated with a higher incidence of DB episodes LocationPatient location may used to determine if the patient is in bed as apart of sleep detection. Altitude Lower oxygen concentration associatedwith high altitudes predisposes patients to more central apnea

In accordance with embodiments of the present invention, once disorderedbreathing is predicted, delivery of coordinated disordered breathingtherapies can be performed. Methods and systems for predictingdisordered breathing and for delivering therapy based on the predictionof disordered breathing are described in commonly owned U.S. patentapplication Ser. No. 10/643,016, filed on Aug. 18, 2003 and Ser. No.10/643,154, filed on Aug. 18, 2003, both of which are incorporatedherein by reference.

FIG. 7 illustrates normal respiration as represented by a signalproduced by a transthoracic impedance sensor. The transthoracicimpedance increases during respiratory inspiration and decreases duringrespiratory expiration. During non-REM sleep, a normal respirationpattern includes regular, rhythmic inspiration—expiration cycles withoutsubstantial interruptions.

In one embodiment, episodes of disordered breathing may be detected bymonitoring the respiratory waveform output of the transthoracicimpedance sensor. When the tidal volume (TV) of the patient'srespiration, as indicated by the transthoracic impedance signal, fallsbelow a hypopnea threshold, then a hypopnea event is declared. Forexample, a hypopnea event may be declared if the patient's tidal volumefalls below about 50% of a recent average tidal volume or other baselinetidal volume value. If the patient's tidal volume falls further to anapnea threshold, e.g., about 10% of the recent average tidal volume orother baseline value, an apnea event is declared.

In another embodiment, detection of disordered breathing involvesdefining and examining a number of respiratory cycle intervals. FIG. 13illustrates respiration intervals used for disordered breathingdetection according to embodiments of the invention. A respiration cycleis divided into an inspiration period corresponding to the patientinhaling, an expiration period, corresponding to the patient exhaling,and a non-breathing period occurring between inhaling and exhaling.Respiration intervals are established using inspiration 1310 andexpiration 1320 thresholds. The inspiration threshold 1310 marks thebeginning of an inspiration period 1330 and is determined by thetransthoracic impedance signal rising above the inspiration threshold1310. The inspiration period 1330 ends when the transthoracic impedancesignal is maximum 1340. A maximum transthoracic impedance signal 1340corresponds to both the end of the inspiration interval 1330 and thebeginning of the expiration interval 1350. The expiration interval 1350continues until the transthoracic impedance falls below an expirationthreshold 1320. A non-breathing interval 1360 starts from the end of theexpiration period 1350 and continues until the beginning of the nextinspiration period 1370.

Detection of sleep apnea and severe sleep apnea according to embodimentsof the invention is illustrated in FIG. 14. The patient's respirationsignals are monitored and the respiration cycles are defined accordingto inspiration 1430, expiration 1450, and non-breathing 1460 intervalsas described in connection with FIG. 13. A condition of sleep apnea isdetected when a non-breathing period 1460 exceeds a first predeterminedinterval 1490, denoted the sleep apnea interval. A condition of severesleep apnea is detected when the non-breathing period 1460 exceeds asecond predetermined interval 1495, denoted the severe sleep apneainterval. For example, sleep apnea may be detected when thenon-breathing interval exceeds about 10 seconds, and severe sleep apneamay be detected when the non-breathing interval exceeds about 20seconds.

Hypopnea is a condition of disordered breathing characterized byabnormally shallow breathing. FIGS. 15A-15B are graphs of tidal volumederived from transthoracic impedance measurements. The graphs comparethe tidal volume of a normal breathing cycle to the tidal volume of ahypopnea episode. FIG. 15A illustrates normal respiration tidal volumeand rate. As shown in FIG. 15B, hypopnea involves a period of abnormallyshallow respiration.

According to an embodiment of the invention, hypopnea is detected bycomparing a patient's respiratory tidal volume to a hypopnea tidalvolume threshold. The tidal volume for each respiration cycle is derivedfrom transthoracic impedance measurements acquired in the mannerdescribed above. The hypopnea tidal volume threshold may be establishedusing clinical results providing a representative tidal volume andduration of hypopnea events. In one configuration, hypopnea is detectedwhen an average of the patient's respiratory tidal volume taken over aselected time interval falls below the hypopnea tidal volume threshold.Furthermore, various combinations of hypopnea cycles, breath intervals,and non-breathing intervals may be used to detect hypopnea, where thenon-breathing intervals are determined as described above.

FIG. 16 is a flowchart illustrating a method of apnea and/or hypopneadetection according to embodiments of the invention. Various parametersare established 1601 before analyzing the patient's respiration fordisordered breathing episodes, including, for example, inspiration andexpiration thresholds, sleep apnea interval, severe sleep apneainterval, and hypopnea tidal volume threshold.

The patient's transthoracic impedance is measured 1605 as described inmore detail above. If the transthoracic impedance exceeds 1610 theinspiration threshold, the beginning of an inspiration interval isdetected 1615. If the transthoracic impedance remains below 1610 theinspiration threshold, then the impedance signal is checked 1605periodically until inspiration 1615 occurs.

During the inspiration interval, the patient's transthoracic impedanceis monitored until a maximum value of the transthoracic impedance isdetected 1620. Detection of the maximum value signals an end of theinspiration period and a beginning of an expiration period 1635.

The expiration interval is characterized by decreasing transthoracicimpedance. When the transthoracic impedance falls 1640 below theexpiration threshold, a non-breathing interval is detected 1655.

If the transthoracic impedance does not exceed 1660 the inspirationthreshold within a first predetermined interval 1665, denoted the sleepapnea interval, then a condition of sleep apnea is detected 1670. Severesleep apnea is detected 1680 if the non-breathing period extends beyonda second predetermined interval 1675, denoted the severe sleep apneainterval.

When the transthoracic impedance exceeds 1660 the inspiration threshold,the tidal volume from the peak-to-peak transthoracic impedance iscalculated, along with a moving average of past tidal volumes 1685. Thepeak-to-peak transthoracic impedance provides a value proportional tothe tidal volume of the respiration cycle. This value is compared to ahypopnea tidal volume threshold 1690. If the peak-to-peak transthoracicimpedance is consistent with the hypopnea tidal volume threshold 1690for a predetermined time 1692, then a hypopnea cycle is detected 1695.

Additional sensors, such as motion sensors, oximetry sensors, and/orposture sensors, may be used to confirm or verify the detection of asleep apnea or hypopnea episode. The additional sensors may be employedto prevent false or missed detections of sleep apnea/hypopnea due toposture and/or motion related artifacts.

Another embodiment of the invention involves classifying respirationpatterns as disordered breathing episodes based on the breath intervalsand/or tidal volumes of one or more respiration cycles within therespiration patterns. According to this embodiment, the duration andtidal volumes associated with a respiration pattern are compared toduration and tidal volume thresholds. The respiration pattern isdetected as a disordered breathing episode based on the comparison.

According to principles of the invention, a breath interval isestablished for each respiration cycle. A breath interval represents theinterval of time between successive breaths, as illustrated in FIG. 17.A breath interval 1730 may be defined in a variety of ways, for example,as the interval of time between successive maxima 1710, 1720 of theimpedance signal waveform.

Detection of disordered breathing, in accordance with embodiments of theinvention, involves the establishment of a duration threshold and atidal volume threshold. If a breath interval exceeds the durationthreshold, an apnea event is detected. Detection of sleep apnea, inaccordance with this embodiment, is illustrated in the graph of FIG. 17.Apnea represents a period of non-breathing. A breath interval 1730exceeding a duration threshold 1740 comprises an apnea episode.

Hypopnea may be detected using the duration threshold and tidal volumethreshold. A hypopnea event represents a period of shallow breathing.Each respiration cycle in a hypopnea event is characterized by a tidalvolume less than the tidal volume threshold. Further, the hypopnea eventinvolves a period of shallow breathing greater than the durationthreshold.

A hypopnea detection approach, in accordance with embodiments of theinvention, is illustrated in FIG. 18. Shallow breathing is detected whenthe tidal volume of one or more breaths is below a tidal volumethreshold 1810. If the shallow breathing continues for an intervalgreater than a duration threshold 1820, then the breathing patternrepresented by the sequence of shallow respiration cycles, is classifiedas a hypopnea event.

FIGS. 19 and 20 provide charts illustrating classification of individualdisordered breathing events and series of periodically recurringdisordered breathing events, respectively. As illustrated in FIG. 19,individual disordered breathing events may be grouped into apnea,hypopnea, tachypnea and other disordered breathing events. Apnea eventsare characterized by an absence of breathing. Intervals of reducedrespiration are classified as hypopnea events. Tachypnea events includeintervals of rapid respiration characterized by an elevated respirationrate.

As illustrated in FIG. 19, apnea and hypopnea events may be furthersubdivided as either central events, related to central nervous systemdysfunction, or obstructive events, caused by upper airway obstruction.A tachypnea event may be further classified as a hyperpnea event,represented by hyperventilation, i.e., rapid deep breathing. A tachypneaevent may alternatively be classified as rapid breathing, typically ofprolonged duration.

FIG. 20 illustrates classification of combinations of periodicallyrecurring disordered breathing events. Periodic breathing may beclassified as obstructive, central or mixed. Obstructive periodicbreathing is characterized by cyclic respiratory patterns with anobstructive apnea or hypopnea event in each cycle. Central periodicbreathing involves cyclic respiratory patterns including a central apneaor hypopnea event in each cycle. Periodic breathing may also be of mixedorigin. Mixed origin periodic breathing is characterized by cyclicrespiratory patterns having a mixture of obstructive and central apneaevents in each cycle. Cheyne-Stokes is a particular type of periodicbreathing involving a gradual waxing and waning of tidal volume andhaving a central apnea and hyperpnea event in each cycle. Othermanifestations of periodic breathing are also possible. Disorderedbreathing episodes may be classified based on the characteristicrespiration patterns associated with particular types of disorderedbreathing.

As illustrated in FIGS. 21A-E, a respiration pattern detected as adisordered breathing episode may include only an apnea respiration cycle2110 (FIG. 21A), only hypopnea respiration cycles 2150 (FIG. 21D), or amixture of hypopnea and apnea respiration cycles 2120 (FIG. 21B), 2130(FIG. 21C), 2160 (FIG. 21E). A disordered breathing event 2120 may beginwith an apnea respiration cycle and end with one or more hypopneacycles. In another pattern, the disordered breathing event 2130 maybegin with hypopnea cycles and end with an apnea cycle. In yet anotherpattern, a disordered breathing event 2160 may begin and end withhypopnea cycles with an apnea cycle in between the hypopnea cycles.

FIG. 22 is a flowchart of a method for detecting disordered breathing inaccordance with embodiments of the invention. The method illustrated inFIG. 22 operates by classifying breathing patterns using breathintervals in conjunction with tidal volume and duration thresholds aspreviously described above. In this example, a duration threshold and atidal volume threshold are established for determining both apnea andhypopnea breath intervals. An apnea episode is detected if the breathinterval exceeds the duration threshold. A hypopnea episode is detectedif the tidal volume of successive breaths remains less than the tidalvolume threshold for a period in excess of the duration threshold. Mixedapnea/hypopnea episodes may also occur. In these cases, the period ofdisordered breathing is characterized by shallow breaths ornon-breathing intervals. During the mixed apnea/hypopnea episodes, thetidal volume of each breath remains less than the tidal volume thresholdfor a period exceeding the duration threshold.

Transthoracic impedance is sensed and used to determine the patient'srespiration cycles. Each breath 2210 may be characterized by a breathinterval, the interval of time between two impedance signal maxima, anda tidal volume (TV).

If a breath interval exceeds 2215 the duration threshold, then therespiration pattern is consistent with an apnea event, and an apneaevent trigger is turned on 2220. If the tidal volume of the breathinterval exceeds 2225 the tidal volume threshold, then the breathingpattern is characterized by two respiration cycles of normal volumeseparated by a non-breathing interval. This pattern represents a purelyapneic disordered breathing event, and apnea is detected 2230. Becausethe final breath of the breath interval was normal, the apnea eventtrigger is turned off 2232, signaling the end of the disorderedbreathing episode. However, if the tidal volume of the breath intervaldoes not exceed 2225 the tidal volume threshold, the disorderedbreathing period is continuing and the next breath is checked 2210.

If the breath interval does not exceed 2215 the duration threshold, thenthe tidal volume of the breath is checked 2235. If the tidal volume doesnot exceed 2235 the tidal volume threshold, the breathing pattern isconsistent with a hypopnea cycle and a hypopnea event trigger is set on2240. If the tidal volume exceeds the tidal volume threshold, then thebreath is normal.

If a period of disordered breathing is in progress, detection of anormal breath signals the end of the disordered breathing. If disorderedbreathing was previously detected 2245, and if the disordered breathingevent duration has not exceeded 2250 the duration threshold, and thecurrent breath is normal, then no disordered breathing event is detected2255. If disordered breathing was previously detected 2245, and if thedisordered breathing event duration has extended for a period of timeexceeding 2250 the duration threshold, and the current breath is normal,then the disordered breathing trigger is turned off 2260. In thissituation, the duration of the disordered breathing episode was ofsufficient duration to be classified as a disordered breathing episode.If an apnea event was previously triggered 2265, then an apnea event isdeclared 2270. If a hypopnea was previously triggered 2265, then ahypopnea event is declared 2275.

As previously discussed in connection with the flowcharts of FIG. 1Babove, the sleep disordered breathing therapy may be modified based oninformation developed using one or more monitored patient conditions.The information may indicate that coordinated sleep disordered breathingtherapy should be initiated, terminated or modified. The information maybe developed based on the severity of the sleep disordered breathing,interactions between the sleep disordered breathing therapy and othertherapies delivered to the patient, the effectiveness of the sleepdisordered breathing therapy, the impact of the sleep disorderedbreathing therapy on the patient, and/or other parameters of thebreathing therapy. Once initiated, the system may continue to monitorpatient conditions to develop feedback information, and the coordinatedbreathing therapy may be modified based on periodically updatedassessments of sleep disordered breathing severity, therapy efficacy,patient comfort during therapy, sleep quality during therapy,interactions between therapies, or other factors, for example.

A subset of patient conditions, for example, one or more of therepresentative conditions listed in Table 1, may be used in connectionwith detecting sleep disordered breathing. Another subset of patientconditions, which may overlap the conditions used sleep disorderedbreathing assessment, may be used in connection with the determining aseverity of disordered breathing. Another subset of patient conditionsmay be used to determine coordinated therapy efficacy. In somescenarios, the severity of disordered breathing may be inversely relatedto coordinated therapy efficacy. Thus it may be possible to use a commonsubset of patient conditions to assess severity of disordered breathingand coordinated therapy efficacy. Other subsets may be used to assessimpact to the patient and/or therapy interactions, for example.

Acute responses to disordered breathing may be used to detect disorderedbreathing and both acute and chronic responses may be used to assess theseverity of the disordered breathing, the efficacy of the therapy and/orimpact of coordinated disordered breathing therapy, for example.Conditions used to assess therapy effectiveness may be different from,or the same as, conditions used to assess an impact of the therapy onthe patient. Table 4 provides a representative set of conditions thatmay be used for therapy assessment with respect to therapyefficacy/disordered breathing severity and therapy impact.

TABLE 4 Condition Therapy Impact Therapy Efficacy/Severity Arousal-BasedMay be used to assess Sleep therapy impact during Fragmentation sleep.Measures Restful sleep May be used to assess (Patient reported) therapyimpact during sleep. Discomfort May be used to assess (Patient reported)therapy impact. Pacing algorithm May be used to assess interactiontherapy impact. Heart Failure May be used to assess May be used toanalyze the (HF)Severity therapy impact. efficacy of therapy to improveheart pumping function. HF severity may be indicated by the apneahypopnea index. Improving apnea via therapy may improve HF condition.Remaining useful May be used to assess life of therapy impact. therapydevice Disturbed May be used to analyze/assess Breathing- efficacy oftherapy to mitigate Based Measures disordered breathing episodes.Respiration May be used to analyze/assess quality efficacy of therapy tomitigate (Patient reported) disordered breathing episodes. Heart rateDisordered breathing causes variability heart rate variability to (HRV)decrease. Therapy may be modified based on changes in HRV Blood pressureDisordered breathing causes blood pressure increase Sympathetic Changesin sympathetic nerve nerve activity are caused by activity (SNA)disordered breathing. Therapy may be adjusted based on the level of SNABlood chemistry A number of disordered breathing related changes mayoccur in a patient's blood chemistry, including, e.g., highernorepinephrine levels, and lower PaCO₂

It is understood that the patient conditions that may be used inconnection the medical systems described herein are not limited to therepresentative sets listed in Tables 1-4 or those described herein.Further, although illustrative sensing methods for detecting the patientconditions listed above are provided, it is understood that the patientconditions may be detected using a wide variety of technologies. Theembodiments and features described in herein are not limited to theparticular patient conditions or the particular sensing technologiesprovided.

In accordance with various embodiments of the invention, conditionsrelated to sleep quality, e.g., sleep fragmentation and/or otherarousal-based measures, patient-reported restful sleep, andpatient-reported discomfort during therapy, may be used to assess theimpact of the therapy on the patient. For example, if a patient isreceiving effective coordinated disordered breathing therapy and has lowsleep fragmentation, reports restful sleep, and reports no discomfort,the adverse effects of the therapy on the patient may be relatively low.If sleep fragmentation is relatively high, or if the patient reportsdiscomfort or feeling tired after sleeping, these conditions mayindicate that coordinated therapy is causing sleep disturbances and/orother undesirable effects.

It is undesirable to provide coordinated therapy that eliminates thedisordered breathing but increases sleep fragmentation. In such asituation, the disordered breathing therapy may exacerbate the adverseeffects produced by the respiratory disturbances. Thus, it may bepreferable to assess the impact of the therapy on the patient and adjustthe therapy to improve sleep quality.

Sleep fragmentation and sleep disruptions may also occur if coordinateddisordered breathing therapy is ineffective and disordered breathingoccurs during sleep. Therefore, a therapy impact assessment based ondetected sleep quality and/or patient-reported restful sleep maypreferably take into account an assessment of therapy effectiveness.

Evaluation of the impact of coordinated disordered breathing therapy onthe patient preferably takes into consideration the impact of disorderedbreathing therapy on the overall therapeutic goals for the patient,including goals associated with other therapies delivered to the patientas well as coordinated sleep disordered breathing therapy goals. Thecoordinated disordered breathing therapy may involve a variety oftherapy regimens implemented to achieve predetermined therapeutic goals.In some embodiments, the effectiveness of the therapy, or the degree towhich the therapy meets one or more therapeutic goals, may be assessedby detecting and analyzing episodes of disordered breathing that occurduring therapy delivery.

For example, a therapeutic goal may involve terminating a disorderedbreathing episode and the coordinated disordered breathing therapy maybe adapted to achieve this goal. Additionally, or alternatively, atherapeutic goal may involve terminating a disordered breathing episodeand preventing further disordered breathing. In this example situation,the therapy a coordinated therapy regimen may be adapted to provide afirst therapy to terminate the disordered breathing episode using afirst therapy device and provide a second preventative therapy to reduceor eliminate further disordered breathing episodes using a secondtherapy device. The second preventative therapy may be adapted to reduceepisodes of disordered breathing below a predetermined disorderedbreathing episode threshold. A disordered breathing episode thresholdmay be expressed, for example, in terms of an apnea/hypopnea index (AHI)or percent time in periodic breathing (% PB).

FIGS. 23 and 24 are flowcharts illustrating methods of adapting acoordinated sleep disordered breathing therapy according to embodimentsof the invention. As previously discussed, the coordinated sleepdisordered breathing therapy may involve one or more of a number oftherapy types. The coordinated sleep disordered breathing therapy mayinvolve, for example, one or more of cardiac pacing therapy,patient-external breathing therapy, nerve stimulation therapy, musclestimulation therapy, and/or drug therapy. Processes for adapting acardiac therapy based on feedback information, are described in commonlyowned U.S. patent application Ser. No. 10/643,203, filed Aug. 18, 2003which is incorporated herein by reference. Similar techniques may beapplied to adjust therapy of different types.

The flowchart of FIG. 23 illustrates a method of providing coordinateddisordered breathing therapy to achieve a desired level of therapyefficacy. In this embodiment, a first set of conditions associated withdisordered breathing is detected 2310 and used to determine if adisordered breathing episode is occurring. If disordered breathing isdetected 2320, coordinated disordered breathing therapy is delivered2330 to the patient to mitigate the disordered breathing. In oneembodiment, the therapy delivered to the patient may involve externalrespiratory therapy. The therapy may initially involve air delivered ata first predetermined pressure.

A second set of conditions associated with therapy effectiveness issensed 2340 and used to assess the effectiveness of the therapy. Thedetected conditions used to assess the efficacy of the therapy and adaptthe therapy to mitigate disordered breathing may represent one or moreof the acute conditions associated with disordered breathing, e.g.,detected episodes of interrupted breathing, hypoxia, arousals, negativeintrathoracic pressure, blood pressure, and heart rate or blood pressuresurges.

Additionally, or alternatively, the conditions used to assess therapyefficacy and adapt the coordinated sleep disordered breathing therapymay include one or more chronic conditions associated with disorderedbreathing, including, for example, decreased heart rate variability,increased blood pressure, chronic changes in sympathetic nerve activity,and changes in blood chemistry, such as increased levels of PaCO₂ andnorepinephrine levels, among others.

In general, a therapeutic goal in the treatment of disordered breathingis to provide the least aggressive therapy that effectively mitigates,terminates or prevents the patient's disordered breathing or achieves aparticular therapeutic goal associated with coordinated disorderedbreathing therapy. In order to achieve the least aggressive therapy anassessment of the efficacy of therapy or assessment of the impact of thetherapy on the patient is performed. According to various embodiments,therapy efficacy may be determined by evaluating one or more patientconditions sensed or acquired using sensors positioned on internal orexternal medical devices and/or remote devices. The therapy regimen maybe adapted based on the determined therapy efficacy to provide the leastaggressive therapy.

For example, in adapting a therapy regimen the system may take intoaccount various conditions for evaluating the impact of the therapy onthe patient such as patient comfort, as indicated by patient feedback,stress on physiological systems involved in the disordered breathingtherapy, interaction with cardiac pacing algorithms, e.g., bradycardiapacing, cardiac resynchronization pacing an/or anti-tachycardia pacing,as determined by interactive effects of the disordered breathing therapywith cardiac pacing, and/or sleep quality, as measured by one or moresleep quality indices, to devise a coordinated disordered breathingtherapy regimen that reduces an impact of the therapy on the patient.

In addition, impact to the patient may involve reduction of the usefulservice life of an implantable therapeutic device used to deliverdisordered breathing therapy and/or pacing therapy for cardiacdysfunction. For example, a level of disordered breathing therapy may beunacceptably high if the energy requirements of the therapy result in anexcessively reduced device service life. In this situation, early deviceremoval and replacement produces a negative impact to the patient.Therefore, therapy to mitigate disordered breathing may be adapted basedon a projected reduction in device useful service life.

In one example, the therapy delivered to mitigate disordered breathingmay be adapted to reduce or adjust interactions between the disorderedbreathing therapy and other therapies delivered to the patient. Forexample, some patients may receive neural stimulation therapy to treatdisordered breathing and cardiac stimulation therapy to treat cardiacdisorders such as bradycardia or congestive heart failure. Interactionsmay occur between the neural stimulation therapy and the patient'scardiac pacing regimen, e.g., pacing for bradycardia or cardiacresynchronization. Such interactions may be factored into the assessmentof the impact disordered breathing therapy on the overall therapydelivered to the patient.

In another example, if the severity of the disordered breathing isdetermined to be severe, and therapy efficacy is lacking, then a moreintense level of coordinated therapy may be initially delivered to thepatient. The coordinated disordered breathing therapy regimen may beenhanced by increasing the intensity or level of one type of therapywhile decreasing the intensity of another type of therapy to moreeffectively mitigate the disordered breathing. Alternatively, where twotherapy types are delivered to the patient, the coordinated disorderedbreathing therapy regimen may be enhanced by increasing or decreasingthe overall intensity or level of therapy in order to decrease theseverity or frequency of disordered breathing episodes, thus reducingundesirable side effects from the therapy and extending the devicelifetime.

If the coordinated therapy effectiveness is acceptable 2350, e.g.,terminates or reduces the patient's disordered breathing or meets someother desired goal, then the coordinated therapy may be adapted 2360 toprovide a less aggressive therapy, e.g., air delivered at a decreasedpressure, cardiac pacing delivered at a higher rate, nerve stimulationdelivered at a lower amplitude. If the coordinated therapy is noteffective 2350, then the coordinated therapy may be adapted 2370 toenhance therapy efficacy by providing a more aggressive therapy regimen,e.g., delivering air at an increased pressure, cardiac pacing deliveredat a lower rate, nerve stimulation delivered at a lower amplitude.

In one embodiment, coordinated therapy may be determined to beineffective if disordered breathing continues unmitigated followingtherapy delivery. In this situation, the therapy may be adapted toprovide a more aggressive therapy. In another embodiment, if thedisordered breathing decreases sufficiently in severity, or is otherwisesufficiently mitigated, the therapy may be enhanced by adapting thetherapy to provide a less aggressive therapy, e.g., decreased airpressure. As previously discussed, a less aggressive therapy ispreferable to reduce the risk of arousal and to provide a morecomfortable therapy to the patient, for example.

The flowchart of FIG. 24 illustrates a method of providing a coordinateddisordered breathing therapy in accordance with embodiments of theinvention. In this example, a first set of conditions associated withdisordered breathing is detected 2410 and used to determine if adisordered breathing episode is occurring. If disordered breathing isdetected 2420, coordinated therapy is delivered 2430 to the patient tomitigate the disordered breathing. The level of therapy initiallydelivered to the patient may be based on a severity of the disorderedbreathing.

A second set of conditions is detected 2440 and used to adapt thetherapy. Based on the second set of sensed conditions, the therapyefficacy is assessed 2445. If the therapy efficacy is not acceptable2450, then the coordinated therapy may be adapted 2460 to enhancetherapy efficacy. If the therapy efficacy is acceptable 2450, then theimpact of the therapy on the patient may be assessed 2470.

If the therapy impact on the patient is acceptable 2480, the systemcontinues to deliver the therapy. When the coordinated therapy regimenis complete 2485, then therapy is terminated 2490. If the therapy impacton the patient exceeds acceptable limits, the therapy impact is notacceptable 2480, and the coordinated therapy may be adapted 2460 toreduce the therapy impact.

The methods illustrated in the flowcharts of FIGS. 23 and 24 contemplatereal-time monitoring of patient conditions allowing the coordinatedtherapy system to coordinate a therapy regimen to accommodate thechanging needs of the patient. In one configuration, the coordinatedtherapy may be adjusted during the period that therapy is delivered tothe patient. In another configuration, the therapy may be adaptedbetween sleep disordered breathing episodes or from night-to-night basedon assessment of therapy delivered in connection with one or morepreviously detected disordered breathing episodes.

Methods, devices, and systems implementing a coordinated approach todisordered breathing treatment and/or monitoring disordered breathingmay incorporate one or more of the features, structures, methods, orcombinations thereof described herein. For example, a medical system maybe implemented to include one or more of the features and/or processesdescribed below. It is intended that such a method, device, or systemneed not include all of the features and functions described herein, butmay be implemented to include one or more selected features andfunctions that provide unique structures and/or functionality.

A number of the examples presented herein involve block diagramsillustrating functional blocks used for coordinated monitoring,diagnosis and/or therapy functions in accordance with embodiments of thepresent invention. It will be understood by those skilled in the artthat there exist many possible configurations in which these functionalblocks can be arranged and implemented. The examples depicted hereinprovide examples of possible functional arrangements used to implementthe approaches of the invention.

It is understood that the components and functionality depicted in thefigures and described herein can be implemented in hardware, software,or a combination of hardware and software. It is further understood thatthe components and functionality depicted as separate or discreteblocks/elements in the figures in general can be implemented incombination with other components and functionality, and that thedepiction of such components and functionality in individual or integralform is for purposes of clarity of explanation, and not of limitation.

What is claimed is:
 1. An automated method for delivering therapy,comprising: delivering a first therapy to a patient to treat arespiratory condition; delivering a second therapy to the patient usingan implantable device; sensing one or more parameters; and coordinatingdelivery of the first therapy and the second therapy by shifting therapyburden from the first therapy or the second therapy to the other of thefirst therapy or the second therapy based on the one or more sensedparameters.
 2. The method of claim 1, wherein the respiratory conditioncomprises sleep disordered breathing.
 3. The method of claim 1, whereinthe one or more parameters comprises prediction of disordered breathing.4. The method of claim 1, wherein the one or more parameters comprisestherapy interaction between the first therapy and the second therapy. 5.The method of claim 1, wherein the one or more parameters comprisespatient usage of the first therapy or the second therapy.
 6. The methodof claim 1, wherein at least one of delivering the first therapy anddelivering the second therapy comprises delivering a nerve stimulationtherapy.
 7. The method of claim 6, wherein delivering the nervestimulation therapy comprises delivering a hypoglossal nerve stimulationtherapy.
 8. The method of claim 1, wherein: sensing the one or moreparameters comprises sensing one or more side effect conditionsaffecting the patient and associated with an impact of one or more ofthe first therapy and the second therapy on the patient; andcoordinating delivery comprises shifting therapy burden from the firsttherapy or the second therapy associated with the side effect conditionto the other of the first therapy or the second therapy.
 9. The methodof claim 1, wherein: sensing the one or more parameters comprisesidentifying an interaction between the first therapy and the secondtherapy on the patient; and coordinating delivery comprises shiftingtherapy burden from the first therapy or the second therapy to the otherof the first therapy or the second therapy based on the interaction. 10.The method of claim 1, wherein: sensing the one or more parameterscomprises determining battery life of the implantable device; andcoordinating delivery comprises shifting therapy burden from the secondtherapy to the first therapy in response to the battery life of theimplantable device.
 11. The method of claim 1, wherein: sensing the oneor more parameters comprises sensing an indication of patient discomfortassociated with delivery of one or more of the first therapy and thesecond therapy on the patient; and coordinating delivery comprisesshifting therapy burden from the first therapy or the second therapyassociated with the indication of patient discomfort to the other of thefirst therapy or the second therapy.
 12. A medical system forcontrolling therapy to treat a respiratory condition comprising: a firsttherapy device configured to deliver a first therapy to a patient; animplantable device configured to deliver a second therapy to thepatient; a sensor system for sensing one or more parameters; andcircuitry in communication with the first therapy device, the seconddevice, and the sensor system, the circuitry configured to coordinatedelivery of the first therapy and the second therapy by shifting therapyburden from the first therapy or the second therapy to the other of thefirst therapy or the second therapy based on the one or more sensedparameters.
 13. The medical system of claim 12, wherein the firsttherapy device comprises a nerve stimulation device.
 14. The medicalsystem of claim 13, wherein the first therapy comprises hypoglossalnerve stimulation.
 15. The medical system of claim 12, wherein at leastone of the first therapy and the second therapy is configured to treatdisordered breathing.
 16. The medical system of claim 12, wherein thecircuitry is further configured to predict sleep disordered breathingbased on the one or more parameters and shift therapy burden from thefirst therapy or the second therapy to the other of the first therapy orthe second therapy based on the sleep disordered breathing prediction.17. The medical system of claim 12, wherein the one or more parameterscomprises usage of the first therapy device.
 18. The medical system ofclaim 12, wherein: the sensor system is configured to sense at least oneor more side effect conditions associated with an impact of one or bothof the first therapy and the second therapy on the patient as the one ormore parameters; and the circuitry is configured to shift therapy burdenfrom the first therapy or the second therapy associated with the sideeffect condition to the other of the first therapy or the secondtherapy.
 19. A medical system, comprising: a first therapy deviceconfigured to deliver a nerve therapy to a patient; a second therapydevice configured to deliver an additional therapy to the patient; asensor system for sensing one or more parameters; and circuitry incommunication with the first therapy device, the second therapy device,and the sensor system, the circuitry configured to coordinate deliveryof the nerve therapy and the additional therapy by shifting therapyburden from the nerve therapy or the additional therapy to the other ofthe nerve therapy or the additional therapy based on the one or moresensed parameters.
 20. The medical system of claim 19, wherein the nervetherapy comprises stimulation of the hypoglossal nerve.